Risk of cardiovascular events following COVID-19 in people with and without pre-existing chronic respiratory disease.

BACKGROUND: COVID-19 is associated with cardiovascular outcomes in the general population, but it is unknown whether people with chronic respiratory disease (CRD) have a higher risk of cardiovascular events post-COVID-19 compared with the general population and, if so, what respiratory-related factors may modify this risk in these people. METHODS: Primary and secondary care data from the National Health Service England were used to define a population of adults in England with COVID-19 (index date) between 1 January 2020 and 30 November 2021. Adjusted Cox proportional hazard regression was used to quantify the association between CRD, asthma-related factors, chronic obstructive pulmonary disease (COPD)-related factors, and risk of cardiovascular events. Asthma-specific factors included baseline asthma control, exacerbations, and inhaled corticosteroid (ICS) dose. COPD-specific risk factors included baseline ICS and exacerbations. Secondary objectives quantified the impact of COVID-19 hospitalisation and vaccine dose on cardiovascular outcomes. RESULTS: Of 3 670 455 people, those with CRD had a higher risk of cardiovascular events [adjusted hazard ratio (HRadj), 1.08; 95% confidence interval (CI) 1.06-1.11], heart failure (HRadj, 1.17; 95% CI, 1.12-1.22), angina (HRadj, 1.13; 95% CI, 1.06-1.20) and pulmonary emboli (HRadj, 1.24; 95% CI, 1.15-1.33) compared with people without CRD. In people with asthma or COPD, baseline exacerbations were associated with a higher risk of cardiovascular outcomes (HRadj, 1.36; 95% CI, 1.27-1.00 and HRadj, 1.35; 95% CI, 1.24-1.46, respectively). Regardless of CRD, the risk of cardiovascular events was lower with increasing COVID-19 vaccine dose. CONCLUSIONS: Higher risk of cardiovascular events post-COVID-19 might be explained by the underlying severity of the CRD, and COVID-19 vaccines were beneficial to both people with and those without CRD with regards to cardiovascualr events.

Factors associated with non-fatal heart failure and atrial fibrillation or flutter within the first 30 days post COPD exacerbation: a nested case-control study.

BACKGROUND: An immediate, temporal risk of heart failure and arrhythmias after a Chronic Obstructive Pulmonary Disease (COPD) exacerbation has been demonstrated, particularly in the first month post-exacerbation. However, the clinical profile of patients who develop heart failure (HF) or atrial fibrillation/flutter (AF) following exacerbation is unclear. Therefore we examined factors associated with people being hospitalized for HF or AF, respectively, following a COPD exacerbation. METHODS: We conducted two nested case-control studies, using primary care electronic healthcare records from the Clinical Practice Research Datalink Aurum linked to Hospital Episode Statistics, Office for National Statistics for mortality, and socioeconomic data (2014-2020). Cases had hospitalization for HF or AF within 30 days of a COPD exacerbation, with controls matched by GP practice (HF 2:1;AF 3:1). We used conditional logistic regression to explore demographic and clinical factors associated with HF and AF hospitalization. RESULTS: Odds of HF hospitalization (1,569 cases, 3,138 controls) increased with age, type II diabetes, obesity, HF and arrhythmia history, exacerbation severity (hospitalization), most cardiovascular medications, GOLD airflow obstruction, MRC dyspnea score, and chronic kidney disease. Strongest associations were for severe exacerbations (adjusted odds ratio (aOR)=6.25, 95%CI 5.10-7.66), prior HF (aOR=2.57, 95%CI 1.73-3.83), age≥80 years (aOR=2.41, 95%CI 1.88-3.09), and prior diuretics prescription (aOR=2.81, 95%CI 2.29-3.45). Odds of AF hospitalization (841 cases, 2,523 controls) increased with age, male sex, severe exacerbation, arrhythmia and pulmonary hypertension history and most cardiovascular medications. Strongest associations were for severe exacerbations (aOR=5.78, 95%CI 4.45-7.50), age≥80 years (aOR=3.15, 95%CI 2.26-4.40), arrhythmia (aOR=3.55, 95%CI 2.53-4.98), pulmonary hypertension (aOR=3.05, 95%CI 1.21-7.68), and prescription of anticoagulants (aOR=3.81, 95%CI 2.57-5.64), positive inotropes (aOR=2.29, 95%CI 1.41-3.74) and anti-arrhythmic drugs (aOR=2.14, 95%CI 1.10-4.15). CONCLUSIONS: Cardiopulmonary factors were associated with hospitalization for HF in the 30 days following a COPD exacerbation, while only cardiovascular-related factors and exacerbation severity were associated with AF hospitalization. Understanding factors will help target people for prevention.

Accuracy of the recording of pneumonia events in English electronic healthcare record data in patients with chronic obstructive pulmonary disease.

BACKGROUND: In primary care, identifying pneumonia events in people with chronic obstructive pulmonary disease (COPD) may be challenging due to similarities in symptoms with COPD exacerbations and lack of diagnostic testing. This study explored the accuracy of pneumonia diagnosis coded in primary care by comparing diagnosis in primary care with diagnosis in hospital. METHODS: A study population of people with COPD in England was created using the Clinical Practice Research Datalink Aurum database linked with Hospital Episode Statistics inpatient data. Pneumonia codes only, and pneumonia code with associated clinical and/or treatment codes (chest x-ray, symptoms, antibiotics, sputum and blood culture) were used to determine pneumonia events in primary care. Events that were followed by hospitalisation within 7 days were used to estimate the positive predictive value (PPV) of pneumonia coding in primary care, using primary diagnosis of pneumonia in secondary care as the gold standard. The PPV of primary care recording of hospitalised pneumonia was also calculated. RESULTS: Two hundred seventy-four thousand one hundred fifty-six COPD patients were eligible for inclusion, of whom 7,560 had an eligible pneumonia event in primary care diagnosed between 2015-2019 which was not 'hospital-acquired' and was diagnosed and entered on the same day. Of the 2,094 events which were followed by hospitalisation within 7 days, 1,208 had a primary diagnosis of pneumonia in hospital, representing a PPV of pneumonia coding in primary care of 57.7% (95% CI 55.6%-59.8%). Another 284 (13.6%) were diagnosed as a COPD exacerbation and 114 (5.4%) were diagnosed as another respiratory disease. Use of additional pneumonia clinical and treatment codes had a modest effect on the PPV but substantially lowered the number of events. Of the 33,603 eligible pneumonia events identified in secondary care, only 11,445 were recorded in primary care within 42 days, representing a sensitivity of 34.1% (95% CI 33.6%-34.6%). CONCLUSIONS: Use of primary care pneumonia codes and associated clinical and treatment codes to determine pneumonia is not recommended due to significant levels of misdiagnosis and many hospitalised events failing to be recorded in primary care.

A Harmonised Approach to Curating Research-Ready Datasets for Asthma, Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD) in England, Wales and Scotland Using Clinical Practice Research Datalink (CPRD), Secure Anonymised Information Linkage (SAIL) Databank and DataLoch.

Background: Electronic healthcare records (EHRs) are an important resource for health research that can be used to improve patient outcomes in chronic respiratory diseases. However, consistent approaches in the analysis of these datasets are needed for coherent messaging, and when undertaking comparative studies across different populations. Methods and Results: We developed a harmonised curation approach to generate comparable patient cohorts for asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) using datasets from within Clinical Practice Research Datalink (CPRD; for England), Secure Anonymised Information Linkage (SAIL; for Wales) and DataLoch (for Scotland) by defining commonly derived variables consistently between the datasets. By working in parallel on the curation methodology used for CPRD, SAIL and DataLoch for asthma, COPD and ILD, we were able to highlight key differences in coding and recording between the databases and identify solutions to enable valid comparisons. Conclusion: Codelists and metadata generated have been made available to help re-create the asthma, COPD and ILD cohorts in CPRD, SAIL and DataLoch for different time periods, and provide a starting point for the curation of respiratory datasets in other EHR databases, expediting further comparable respiratory research.

Temporal Risk of Nonfatal Cardiovascular Events After Chronic Obstructive Pulmonary Disease Exacerbation: A Population-based Study.

Rationale: Cardiovascular events after chronic obstructive pulmonary disease (COPD) exacerbations are recognized. Studies to date have been post hoc analyses of trials, did not differentiate exacerbation severity, included death in the cardiovascular outcome, or had insufficient power to explore individual outcomes temporally.Objectives: We explore temporal relationships between moderate and severe exacerbations and incident, nonfatal hospitalized cardiovascular events in a primary care-derived COPD cohort.Methods: We included people with COPD in England from 2014 to 2020, from the Clinical Practice Research Datalink Aurum primary care database. The index date was the date of first COPD exacerbation or, for those without exacerbations, date upon eligibility. We determined composite and individual cardiovascular events (acute coronary syndrome, arrhythmia, heart failure, ischemic stroke, and pulmonary hypertension) from linked hospital data. Adjusted Cox regression models were used to estimate average and time-stratified adjusted hazard ratios (aHRs).Measurements and Main Results: Among 213,466 patients, 146,448 (68.6%) had any exacerbation; 119,124 (55.8%) had moderate exacerbations, and 27,324 (12.8%) had severe exacerbations. A total of 40,773 cardiovascular events were recorded. There was an immediate period of cardiovascular relative rate after any exacerbation (1-14 d; aHR, 3.19 [95% confidence interval (CI), 2.71-3.76]), followed by progressively declining yet maintained effects, elevated after one year (aHR, 1.84 [95% CI, 1.78-1.91]). Hazard ratios were highest 1-14 days after severe exacerbations (aHR, 14.5 [95% CI, 12.2-17.3]) but highest 14-30 days after moderate exacerbations (aHR, 1.94 [95% CI, 1.63-2.31]). Cardiovascular outcomes with the greatest two-week effects after a severe exacerbation were arrhythmia (aHR, 12.7 [95% CI, 10.3-15.7]) and heart failure (aHR, 8.31 [95% CI, 6.79-10.2]).Conclusions: Cardiovascular events after moderate COPD exacerbations occur slightly later than after severe exacerbations; heightened relative rates remain beyond one year irrespective of severity. The period immediately after an exacerbation presents a critical opportunity for clinical intervention and treatment optimization to prevent future cardiovascular events.

The Relationship Between Cardiac Troponin in People Hospitalised for Exacerbation of COPD and Major Adverse Cardiac Events (MACE) and COPD Readmissions.

Background: No single biomarker currently risk stratifies chronic obstructive pulmonary disease (COPD) patients at the time of an exacerbation, though previous studies have suggested that patients with elevated troponin at exacerbation have worse outcomes. This study evaluated the relationship between peak cardiac troponin and subsequent major adverse cardiac events (MACE) including all-cause mortality and COPD hospital readmission, among patients admitted with COPD exacerbation. Methods: Data from five cross-regional hospitals in England were analysed using the National Institute of Health Research Health Informatics Collaborative (NIHR-HIC) acute coronary syndrome database (2008-2017). People hospitalised with a COPD exacerbation were included, and peak troponin levels were standardised relative to the 99th percentile (upper limit of normal). We used Cox Proportional Hazard models adjusting for age, sex, laboratory results and clinical risk factors, and implemented logarithmic transformation (base-10 logarithm). The primary outcome was risk of MACE within 90 days from peak troponin measurement. Secondary outcome was risk of COPD readmission within 90 days from peak troponin measurement. Results: There were 2487 patients included. Of these, 377 (15.2%) patients had a MACE event and 203 (8.2%) were readmitted within 90 days from peak troponin measurement. A total of 1107 (44.5%) patients had an elevated troponin level. Of 1107 patients with elevated troponin at exacerbation, 256 (22.8%) had a MACE event and 101 (9.0%) a COPD readmission within 90 days from peak troponin measurement. Patients with troponin above the upper limit of normal had a higher risk of MACE (adjusted HR 2.20, 95% CI 1.75-2.77) and COPD hospital readmission (adjusted HR 1.37, 95% CI 1.02-1.83) when compared with patients without elevated troponin. Conclusion: An elevated troponin level at the time of COPD exacerbation may be a useful tool for predicting MACE in COPD patients. The relationship between degree of troponin elevation and risk of future events is complex and requires further investigation.

Investigating the prognostic value of digital mobility outcomes in patients with chronic obstructive pulmonary disease: a systematic literature review and meta-analysis.

BACKGROUND: Reduced mobility is a central feature of COPD. Assessment of mobility outcomes that can be measured digitally (digital mobility outcomes (DMOs)) in daily life such as gait speed and steps per day is increasingly possible using devices such as pedometers and accelerometers, but the predictive value of these measures remains unclear in relation to key outcomes such as hospital admission and survival. METHODS: We conducted a systematic review, nested within a larger scoping review by the MOBILISE-D consortium, addressing DMOs in a range of chronic conditions. Qualitative and quantitative analysis considering steps per day and gait speed and their association with clinical outcomes in COPD patients was performed. RESULTS: 21 studies (6076 participants) were included. Nine studies evaluated steps per day and 11 evaluated a measure reflecting gait speed in daily life. Negative associations were demonstrated between mortality risk and steps per day (per 1000 steps) (hazard ratio (HR) 0.81, 95% CI 0.75-0.88, p<0.001), gait speed (<0.80 m·s-1) (HR 3.55, 95% CI 1.72-7.36, p<0.001) and gait speed (per 1.0 m·s-1) (HR 7.55, 95% CI 1.11-51.3, p=0.04). Fewer steps per day (per 1000) and slow gait speed (<0.80 m·s-1) were also associated with increased healthcare utilisation (HR 0.80, 95% CI 0.72-0.88, p<0.001; OR 3.36, 95% CI 1.42-7.94, p=0.01, respectively). Available evidence was of low-moderate quality with few studies eligible for meta-analysis. CONCLUSION: Daily step count and gait speed are negatively associated with mortality risk and other important outcomes in people with COPD and therefore may have value as prognostic indicators in clinical trials, but the quantity and quality of evidence is limited. Larger studies with consistent methodologies are called for.

Prevalence of Poorly Controlled Asthma and Factors Associated with Specialist Referral in Those with Poorly Controlled Asthma in a Paediatric Asthma Population.

Background: Significant morbidity and mortality are associated with poor asthma control. The aim of this study was to determine factors associated with poor control and referral to specialist secondary care services. Methods: We used primary care data from the Clinical Practice Research Datalink Aurum (CPRD) linked with Hospital Episode Statistics (HES) records from 1st January 2007 to 31st December 2019. We selected patients aged 6-17 years old. Poor control was defined as six or more prescriptions of short-acting beta-agonist (SABA) inhalers, two or more courses of oral corticosteroids (OCS), an Asthma Control test (ACT) or childhood ACT <20, one hospital admission for asthma, or one visit to Accident & Emergency (A&E) department for asthma-related episodes in the 12 months following asthma diagnosis. Asthma severity was defined following GINA guidelines 2021. Results: About 17.6% of children aged between 6 and 17 years with active asthma had poor control. Severe asthma, eczema, food allergies, increased BMI and living in deprived areas were identified as risk factors for poor control. Among those with poor control, referral rates to specialist care were extremely low, only 2% overall. Those with severe asthma were three-times more likely to be referred than those with mild-to-moderate asthma [HRcrude = 4.04 (95% CI, 3.35-4.87); HRadj = 2.72 (95% CI: 2.13-3.49)]. Other factors associated with referral were food allergy and living in a more deprived area. Conclusion: Around 1 in 6 children and adolescents with active asthma are not achieving adequate control of their symptoms. Among the subset of 6-17-year olds with poorly controlled asthma, timely referral for specialist advice in secondary care is rare, especially in those with so-called mild asthma who nevertheless are at significant risk for poor asthma outcomes.

Development of an Asthma Exacerbation Risk Prediction Model for Conversational Use by Adults in England.

Background: Improving accurate risk assessment of asthma exacerbations, and reduction via relevant behaviour change among people with asthma could save lives and reduce health care costs. We developed a simple personalised risk prediction model for asthma exacerbations using factors collected in routine healthcare data for use in a risk modelling feature for automated conversational systems. Methods: We used pseudonymised primary care electronic healthcare records from the Clinical Practice Research Datalink (CPRD) Aurum database in England. We combined variables for prediction of asthma exacerbations using logistic regression including age, gender, ethnicity, Index of Multiple Deprivation, geographical region and clinical variables related to asthma events. Results: We included 1,203,741 patients divided into three cohorts to implement temporal validation: 898,763 (74.7%) in the training sample, 226,754 (18.8%) in the testing sample and 78,224 (6.5%) in the validation sample. The Area under the ROC curve (AUC) for the full model was 0.72 and for the restricted model was 0.71. Using a cut-off point of 0.1, approximately 27 asthma reviews by clinicians per 100 patients would be prevented compared with a strategy that all patients are regarded as high risk. Compared with patients without an exacerbation, patients who exacerbated were older, more likely to be female, prescribed more SABA and ICS in the preceding 12 months, have history of GORD, COPD, anxiety, depression, live in very deprived areas and have more severe disease. Conclusion: Using information available from routinely collected electronic healthcare record data, we developed a model that has moderate ability to separate patients who had an asthma exacerbation within 3 months from their index date from patients who did not. When comparing this model with a simplified model with variables that can easily be self-reported through a WhatsApp chatbot, we have shown that the predictive performance of the model is not substantially different.

Recent trends in asthma diagnosis, preschool wheeze diagnosis and asthma exacerbations in English children and adolescents: a SABINA Jr study.

BACKGROUND: Asthma-related burden remains poorly characterised in children in the UK. We quantified recent trends in asthma prevalence and burden in a UK population-based cohort (1‒17-year-olds). METHODS: The Clinical Practice Research Datalink Aurum database (2008‒2018) was used to assess annual asthma incidence and prevalence in 1‒17-year-olds and preschool wheeze in 1‒5-year-olds, stratified by sex and age. During the same period, annual asthma exacerbation rates were assessed in those with either a diagnosis of preschool wheeze or asthma. RESULTS: Annual asthma incidence rates decreased by 51% from 1403.4 (95% CI 1383.7 to 1423.2) in 2008 to 688.0 (95% CI 676.3 to 699.9) per 105 person-years (PYs) in 2018, with the most pronounced decrease observed in 1‒5-year olds (decreasing by 65%, from 2556.9 (95% CI 2509.8 to 2604.7) to 892.3 (95% CI 866.9 to 918.3) per 105 PYs). The corresponding decreases for the 6‒11- and 12‒17-year-olds were 36% (1139.9 (95% CI 1110.6 to 1169.7) to 739.9 (95% CI 720.5 to 759.8)) and 20% (572.3 (95% CI 550.4 to 594.9) to 459.5 (95% CI 442.9 to 476.4)) per 105 PYs, respectively. The incidence of preschool wheeze decreased over time and was slightly more pronounced in the 1‒3 year-olds than in the 4-year-olds. Prevalence of asthma and preschool wheeze also decreased over time, from 18.0% overall in 2008 to 10.2% in 2018 for asthma. Exacerbation rates increased over time from 1.33 (95% CI 1.31 to 1.35) per 10 PYs in 2008 to 1.81 (95% CI 1.78 to 1.83) per 10 PYs in 2018. CONCLUSION: Paediatric asthma incidence decreased in the UK since 2008, particularly in 1-5-year-olds; this was accompanied by a decline in asthma prevalence. Preschool wheeze incidence also decreased in this age group. However, exacerbation rates have been increasing.

Evaluation of data processing pipelines on real-world electronic health records data for the purpose of measuring patient similarity.

BACKGROUND: The ever-growing size, breadth, and availability of patient data allows for a wide variety of clinical features to serve as inputs for phenotype discovery using cluster analysis. Data of mixed types in particular are not straightforward to combine into a single feature vector, and techniques used to address this can be biased towards certain data types in ways that are not immediately obvious or intended. In this context, the process of constructing clinically meaningful patient representations from complex datasets has not been systematically evaluated. AIMS: Our aim was to a) outline and b) implement an analytical framework to evaluate distinct methods of constructing patient representations from routine electronic health record data for the purpose of measuring patient similarity. We applied the analysis on a patient cohort diagnosed with chronic obstructive pulmonary disease. METHODS: Using data from the CALIBER data resource, we extracted clinically relevant features for a cohort of patients diagnosed with chronic obstructive pulmonary disease. We used four different data processing pipelines to construct lower dimensional patient representations from which we calculated patient similarity scores. We described the resulting representations, ranked the influence of each individual feature on patient similarity and evaluated the effect of different pipelines on clustering outcomes. Experts evaluated the resulting representations by rating the clinical relevance of similar patient suggestions with regard to a reference patient. RESULTS: Each of the four pipelines resulted in similarity scores primarily driven by a unique set of features. It was demonstrated that data transformations according to each pipeline prior to clustering can result in a variation of clustering results of over 40%. The most appropriate pipeline was selected on the basis of feature ranking and clinical expertise. There was moderate agreement between clinicians as measured by Cohen's kappa coefficient. CONCLUSIONS: Data transformation has downstream and unforeseen consequences in cluster analysis. Rather than viewing this process as a black box, we have shown ways to quantitatively and qualitatively evaluate and select the appropriate preprocessing pipeline.

Short-acting ß2-agonists and exacerbations in children with asthma in England: SABINA Junior.

Background: Prescription of three or more short-acting ß2-agonist (SABA) canisters per year in adult and adolescent asthma populations is associated with a risk of severe exacerbations; however, evidence in children aged <12 years is limited. Methods: This study analysed data on children and adolescents with asthma in three age cohorts: 1‒5 years, 6‒11 years and 12‒17 years from the Clinical Practice Research Datalink Aurum database for the period 1 January 2007 to 31 December 2019. Associations between SABA prescriptions (three or more versus fewer than three canisters per year) at baseline, defined as 6 months after an asthma diagnosis as a binary exposure variable, and the rate of future asthma exacerbations, defined as oral corticosteroid burst therapy, an emergency department visit or hospital admission, were assessed by multilevel negative binomial regression, adjusted for relevant demographic and clinical confounders. Results: Overall 48 560, 110 091 and 111 891 paediatric patients with asthma were aged 1‒5, 6‒11 and 12‒17 years, respectively. During the baseline period, 22 423 (46.2%), 42 137 (38.3%) and 40 288 (36.0%) in these three age cohorts, respectively, were prescribed three or more SABA canisters per year. Across all age ranges, the rate of future asthma exacerbations in those prescribed three or more versus fewer than three SABA canisters per year was at least two-fold higher. >30% of patients across all age cohorts were not prescribed inhaled corticosteroids (ICS), and the median proportion of days covered was only 33%, suggesting inadequate prescribing of ICS. Conclusion: In children, higher SABA prescriptions at baseline were associated with increased future exacerbation rates. These findings highlight the need for monitoring prescription of three or more SABA canisters per year to identify children with asthma at risk of exacerbations.

Assessing the Feasibility of a Text-Based Conversational Agent for Asthma Support: Protocol for a Mixed Methods Observational Study.

BACKGROUND: Despite efforts, the UK death rate from asthma is the highest in Europe, and 65% of people with asthma in the United Kingdom do not receive the professional care they are entitled to. Experts have recommended the use of digital innovations to help address the issues of poor outcomes and lack of care access. An automated SMS text messaging-based conversational agent (ie, chatbot) created to provide access to asthma support in a familiar format via a mobile phone has the potential to help people with asthma across demographics and at scale. Such a chatbot could help improve the accuracy of self-assessed risk, improve asthma self-management, increase access to professional care, and ultimately reduce asthma attacks and emergencies. OBJECTIVE: The aims of this study are to determine the feasibility and usability of a text-based conversational agent that processes a patient's text responses and short sample voice recordings to calculate an estimate of their risk for an asthma exacerbation and then offers follow-up information for lowering risk and improving asthma control; assess the levels of engagement for different groups of users, particularly those who do not access professional services and those with poor asthma control; and assess the extent to which users of the chatbot perceive it as helpful for improving their understanding and self-management of their condition. METHODS: We will recruit 300 adults through four channels for broad reach: Facebook, YouGov, Asthma + Lung UK social media, and the website Healthily (a health self-management app). Participants will be screened, and those who meet inclusion criteria (adults diagnosed with asthma and who use WhatsApp) will be provided with a link to access the conversational agent through WhatsApp on their mobile phones. Participants will be sent scheduled and randomly timed messages to invite them to engage in dialogue about their asthma risk during the period of study. After a data collection period (28 days), participants will respond to questionnaire items related to the quality of the interaction. A pre- and postquestionnaire will measure asthma control before and after the intervention. RESULTS: This study was funded in March 2021 and started in January 2022. We developed a prototype conversational agent, which was iteratively improved with feedback from people with asthma, asthma nurses, and specialist doctors. Fortnightly reviews of iterations by the clinical team began in September 2022 and are ongoing. This feasibility study will start recruitment in January 2023. The anticipated completion of the study is July 2023. A future randomized controlled trial will depend on the outcomes of this study and funding. CONCLUSIONS: This feasibility study will inform a follow-up pilot and larger randomized controlled trial to assess the impact of a conversational agent on asthma outcomes, self-management, behavior change, and access to care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/42965.

Relationship between asthma and severe COVID-19: a national cohort study.

BACKGROUND: We aimed to determine whether children and adults with poorly controlled or more severe asthma have greater risk of hospitalisation and/or death from COVID-19. METHODS: We used individual-level data from the Office for National Statistics Public Health Data Asset, based on the 2011 census in England, and the General Practice Extraction Service data for pandemic planning and research linked to death registration records and Hospital Episode Statistics admission data. Adults were followed from 1 January 2020 to 30 September 2021 for hospitalisation or death from COVID-19. For children, only hospitalisation was included. RESULTS: Our cohort comprised 35 202 533 adults and 2 996 503 children aged 12-17 years. After controlling for sociodemographic factors, pre-existing health conditions and vaccine status, the risk of death involving COVID-19 for adults with asthma prescribed low dose inhaled corticosteroids (ICS) was not significantly different from those without asthma. Adults with asthma prescribed medium and high dosage ICS had an elevated risk of COVID-19 death; HRs 1.18 (95% CI 1.14 to 1.23) and 1.36 (95% CI 1.28 to 1.44), respectively. A similar pattern was observed for COVID-19 hospitalisation; fully adjusted HRs 1.53 (95% CI 1.50 to 1.56) and 1.52 (95% CI 1.46 to 1.56) for adults with asthma prescribed medium and high-dosage ICS, respectively. Risk of hospitalisation was greater for children with asthma prescribed one (2.58 (95% CI 1.82 to 3.66)) or two or more (3.80 (95% CI 2.41 to 5.95)) courses of oral corticosteroids in the year prior to the pandemic. DISCUSSION: People with mild and/or well-controlled asthma are neither at significantly increased risk of hospitalisation with nor more likely to die from COVID-19 than adults without asthma.

Impact of COPD and asthma on in-hospital mortality and management of patients with heart failure in England and Wales: an observational analysis.

OBJECTIVE: To evaluate the association between having concomitant chronic obstructive pulmonary disease (COPD) or asthma, and in-patient mortality and post-discharge management among patients hospitalised for acute heart failure (HF). SETTING: Data were obtained from patients enrolled in the National Heart Failure Audit. PARTICIPANTS: 217 329 patients hospitalised for HF in England-Wales between March 2012 and 2018. OUTCOMES: In-hospital mortality, referrals to cardiology follow-up and prescriptions for HF medications were compared between patients with comorbid COPD (COPD-HF) or asthma (asthma-HF) versus HF-alone using mixed-effects logistic regression. RESULTS: Patients with COPD-HF were more likely to die during hospitalisation, and those with asthma-HF had a reduced likelihood of death, compared with patients who had HF-alone ((adjusted)ORadj, 95% CI: 1.10, 1.06 to 1.14 and ORadj, 95% CI: 0.84, 0.79 to 0.88). In patients who survived to discharge, referral to HF follow-up services differed between groups: patients with COPD-HF had reduced odds of cardiology follow-up (ORadj, 95% CI 0.79, 0.77 to 0.81), while cardiology referral odds for asthma-HF were similar to HF-alone. Overall, proportions of HF medication prescriptions at discharge were low for both COPD-HF and asthma-HF groups, particularly prescriptions for beta-blockers. CONCLUSIONS: In this nationwide analysis, we showed that COPD and asthma significantly impact the clinical course in patients hospitalised for HF. COPD is associated with higher in-patient mortality and lower cardiology referral odds, while COPD and asthma are both associated with lower use of prognostic HF therapies on discharge. These data highlight therapeutic gaps and a need for better integration of cardiopulmonary services to improve healthcare provision for patients with HF and coexisting respiratory disease.

Left-sided heart failure burden and mortality in idiopathic pulmonary fibrosis: a population-based study.

BACKGROUND: Cardiovascular disease is prevalent in idiopathic pulmonary fibrosis (IPF), yet the extent of left-sided heart failure (HF) burden, whether this has changed with time and whether HF impacts mortality risk in these patients are unknown. The aims of this study were therefore to determine the temporal trends in incidence and prevalence of left-sided HF in patients with IPF in England and compare these to published estimates in the general population and those with comparable chronic respiratory conditions such as chronic obstructive pulmonary disease (COPD), as well as determine the risk of all-cause and cause-specific mortality in patients with comorbid left-sided HF and IPF at population-level using electronic healthcare data. METHODS: Clinical Practice Research Datalink (CPRD) Aurum primary-care data linked to mortality and secondary-care data was used to identify IPF patients in England. Left-sided HF prevalence and incidence rates were calculated for each calendar year between 2010 and 2019, stratified by age and sex. Risk of all-cause, cardiovascular and IPF-specific mortality was calculated using multivariate Cox regression. RESULTS: From 40,577patients with an IPF code in CPRD Aurum, 25, 341 IPF patients met inclusion criteria. Left-sided HF prevalence decreased from 33.4% (95% CI 32.2-34.6) in 2010 to 20.9% (20.0-21.7) in 2019. Left-sided HF incidence rate per 100 person-years (95% CI) remained stable between 2010 and 2017 but decreased from 4.3 (3.9-4.8) in 2017 to 3.4 (3.0-3.9) in 2019. Throughout follow-up, prevalence and incidence were higher in men and with increasing age. Comorbid HF was associated with poorer survival (adjusted HR (95%CI) 1.08 (1.03-1.14) for all-cause mortality; 1.32 (1.09-1.59) for cardiovascular mortality). CONCLUSION: Left-sided HF burden in IPF patients in England remains high, with incidence almost 4 times higher than in COPD, a comparable lung disease with similar cardiovascular risk factors. Comorbid left-sided HF is also a poor prognostic marker. More substantial reduction in left-sided HF prevalence than incidence suggests persistently high IPF mortality. Given rising IPF incidence in the UK, this calls for better management of comorbidities such as left-sided HF to help optimise IPF survival.

Gang Members, Gang Affiliates, and Violent Men: Perpetration of Social Harms, Violence-Related Beliefs, Victim Types, and Locations.

Adult gang involvement attracts little empirical attention, so little is known about how they compare to nongang violent men in social harms beyond gang contexts. This study, based on unpublished data of 1,539 adult males, aged 19 to 34, from the Coid et al. national survey, compared gang members' (embedded in a gang; n = 108), affiliates' (less embedded in a gang; n = 119), and violent men's (no gang association; n = 1,312) perpetration of social harms by assessing their violence-related dispositions and beliefs, victim types, and locations of violence. Results showed that compared with violent men, gang members and affiliates were equally more likely to: cause social harms to a wider range of victims, including family and friends; seek violence; be excited by violence; and carry weapons. Gang members and affiliates were equally more likely than violent men to be violent at home, in friends' homes, and at work; they also thought about hurting people, but felt regret for some of their violence. A decreasing gradient was identified in gang members' (highest), affiliates' (next highest) and violent men's (lowest) beliefs in violent retaliation when disrespected, the use of violence instrumentally and when angry, and worry about being violently victimized. Implications of findings are that interventions need to address anger issues across all levels of adult gang membership. Importantly, adult gang members' regrets regarding violence and anxiety about being violently victimized could be key factors that interventions could use to help them relinquish their gang involvement.

GP consultation rates for sequelae after acute covid-19 in patients managed in the community or hospital in the UK: population based study.

OBJECTIVES: To describe the rates for consulting a general practitioner (GP) for sequelae after acute covid-19 in patients admitted to hospital with covid-19 and those managed in the community, and to determine how the rates change over time for patients in the community and after vaccination for covid-19. DESIGN: Population based study. SETTING: 1392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database. PARTICIPANTS: 456 002 patients with a diagnosis of covid-19 between 1 August 2020 and 14 February 2021 (44.7% men; median age 61 years), admitted to hospital within two weeks of diagnosis or managed in the community, and followed-up for a maximum of 9.2 months. A negative control group included individuals without covid-19 (n=38 511) and patients with influenza before the pandemic (n=21 803). MAIN OUTCOME MEASURES: Comparison of rates for consulting a GP for new symptoms, diseases, prescriptions, and healthcare use in individuals admitted to hospital and those managed in the community, separately, before and after covid-19 infection, using Cox regression and negative binomial regression for healthcare use. The analysis was repeated for the negative control and influenza cohorts. In individuals in the community, outcomes were also described over time after a diagnosis of covid-19, and compared before and after vaccination for individuals who were symptomatic after covid-19 infection, using negative binomial regression. RESULTS: Relative to the negative control and influenza cohorts, patients in the community (n=437 943) had significantly higher GP consultation rates for multiple sequelae, and the most common were loss of smell or taste, or both (adjusted hazard ratio 5.28, 95% confidence interval 3.89 to 7.17, P<0.001); venous thromboembolism (3.35, 2.87 to 3.91, P<0.001); lung fibrosis (2.41, 1.37 to 4.25, P=0.002), and muscle pain (1.89, 1.63 to 2.20, P<0.001); and also for healthcare use after a diagnosis of covid-19 compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients in the community were joint pain (2.5%), anxiety (1.2%), and prescriptions for non-steroidal anti-inflammatory drugs (1.2%). Patients admitted to hospital (n=18 059) also had significantly higher GP consultation rates for multiple sequelae, most commonly for venous thromboembolism (16.21, 11.28 to 23.31, P<0.001), nausea (4.64, 2.24 to 9.21, P<0.001), prescriptions for paracetamol (3.68, 2.86 to 4.74, P<0.001), renal failure (3.42, 2.67 to 4.38, P<0.001), and healthcare use after a covid-19 diagnosis compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients admitted to hospital were venous thromboembolism (3.5%), joint pain (2.7%), and breathlessness (2.8%). In patients in the community, anxiety and depression, abdominal pain, diarrhoea, general pain, nausea, chest tightness, and tinnitus persisted throughout follow-up. GP consultation rates were reduced for all symptoms, prescriptions, and healthcare use, except for neuropathic pain, cognitive impairment, strong opiates, and paracetamol use in patients in the community after the first vaccination dose for covid-19 relative to before vaccination. GP consultation rates were also reduced for ischaemic heart disease, asthma, and gastro-oesophageal disease. CONCLUSIONS: GP consultation rates for sequelae after acute covid-19 infection differed between patients with covid-19 who were admitted to hospital and those managed in the community. For individuals in the community, rates of some sequelae decreased over time but those for others, such as anxiety and depression, persisted. Rates of some outcomes decreased after vaccination in this group.

Care After Presenting with Seizures (CAPS): An analysis of the impact of a seizure referral pathway and nurse support on neurology referral rates for patients admitted with a seizure.

INTRODUCTION: The National Audit of Seizure Management in Hospitals (NASH) identified low referral rates to neurology and epilepsy services after an emergency department attendance or admission with a seizure. METHODS: National Health Service Secondary Users Service (SUS) data were used to assess the impact of a seizure pathway at seven hospitals in Cheshire & Merseyside, which was implemented in 2014. Three of these hospitals also had a nurse employed part-time to support the pathway. Patients admitted with a seizure between 2011 and 2018 inclusive were identified using an algorithm based on ICD-10 codes, and the primary outcome was a neurology referral within 3 months of admission. Regression models were used to assess the impact of age, deprivation and comorbidity on post admission clinic referral rates. RESULTS: 13,285 admissions with seizure were included in the analysis. 5,677 had not attended a neurology clinic appointment in the 12 months before the admission. The percentage of whom that were offered an appointment following the admission was: 16.0% before the pathway and 35.9% with the nurse-supported pathway, which was significant in the regression model. 4,700 admissions had attended a neurology clinic appointment in the 12 months before the admission. Of this group, the percentage of whom that were offered an appointment following the admission was: 55.2% before the pathway and 62.4% with the nurse-supported pathway, an increase that was not significant in the regression model. The regression models identified significant health inequalities whereby older patients, those with comorbidities and those living in deprived areas were significantly less likely to be referred. CONCLUSION: Neurology out-patient appointment rates following an admission with seizures are low, worryingly so for those with no neurology appointment in the previous 12 months. A nurse-supported pathway can improve appointment rates, but the effect is modest. Further service redesign is required; the impact of which should be rigorously evaluated.

Heterogeneity in outcome assessment for inflammatory bowel disease in routine clinical practice: a mixed-methods study in a sample of English hospitals.

OBJECTIVES: Knowledge of the extent of variation in outcome assessment for inflammatory bowel disease (IBD) in routine practice is limited. We aimed to describe and quantify variation in outcome coverage and to explore patient, clinician and practitioner factors associated with it. DESIGN: Prospective exploratory mixed-methods study. SETTING: IBD clinics at six hospitals in North West England with differing electronic health record (EHR) systems. METHODS: Mixed-methods study comprising: (a) structured observations of outcomes elicited during consultations (102 patients consulting 24 clinicians); (b) retrospective analysis of outcomes recorded in the EHR (909 consultations; 127 clinicians) and (c) semistructured interviews with the 24 observed clinicians. We determined whether specific outcome 'sets' were elicited or recorded, including: (1) a minimum set of symptom pairs ('PRO-2'); (2) symptom sets from disease activity indices and (3) a reference list of 37 symptoms, signs and impacts. Factors associated with variation were explored in univariate and multivariate binary logistic regression analyses and from clinician interviews. RESULTS: PRO-2 coverage was not invariable (elicited during 81% of observed consultations; recorded in 56% of EHR) and infrequent for complete activity indices (all domains from Harvey-Bradshaw Index: elicited, 18%; recorded, 5%). The median number of outcomes from the reference list elicited per consultation was 12 (13-fold variation) and recorded in EHR was 7 (>20-fold variation). Symptom quantification (PRO-2) seldom adhered closely to standardised descriptors and an explicit timeframe was defined rarely. PRO-2 recording in EHR was associated with a diagnosis of ulcerative colitis (OR: 2.09 (95% CI 1.15 to 3.80)) and nurse-led consultations (OR: 6.98 (95% CI 3.28 to 14.83)) and a three-way model suggested 26% of total variability lay between clinicians, 17% between patients but the remainder was unexplained. Most clinicians expressed preference for individualised health status evaluations versus standardised outcome assessments. CONCLUSIONS: There was little evidence for standardised assessment and recording of IBD outcomes and substantial intra-clinician and inter-clinician variation from one consultation to another. Nurses demonstrated a greater tendency to standardised practice.