Clinician views on how clinical decision support systems can help diagnose asthma in primary care: a qualitative study.

OBJECTIVE: Asthma can be difficult to diagnose in primary care. Clinical decision support systems (CDSS) can assist clinicians when making diagnostic decisions, but the perspectives of intended users need to be incorporated into the software if the CDSS is to be clinically useful. Therefore, we aimed to understand health professional views on the value of an asthma diagnosis CDSS and the barriers and facilitators for use in UK primary care. METHODS: We recruited doctors and nurses working in UK primary care who had experience of assessing respiratory symptoms and diagnosing asthma. Qualitative interviews were used to explore clinicians' experiences of making a diagnosis of asthma and understand views on a CDSS to support asthma diagnosis. Interviews were audio-recorded, transcribed verbatim and analyzed thematically. RESULTS: 16 clinicians (nine doctors, seven nurses) including 13 participants with over 10 years experience, contributed interviews. Participants saw the potential for a CDSS to support asthma diagnosis in primary care by structuring consultations, identifying relevant information from health records, and having visuals to communicate findings to patients. Being evidence based, regularly updated, integrated with software, quick and easy to use were considered important for a CDSS to be successfully implemented. Experienced clinicians were unsure a CDSS would help their routine practice, particularly in straightforward diagnostic scenarios, but thought a CDSS would be useful for trainees or less experienced colleagues. CONCLUSIONS: To be adopted into clinical practice, clinicians were clear that a CDSS must be validated, integrated with existing software, and quick and easy to use.

Quality of ethnicity data within Scottish health records and implications of misclassification for ethnic inequalities in severe COVID-19: a national linked data study.

BACKGROUND: We compared the quality of ethnicity coding within the Public Health Scotland Ethnicity Look-up (PHS-EL) dataset, and other National Health Service datasets, with the 2011 Scottish Census. METHODS: Measures of quality included the level of missingness and misclassification. We examined the impact of misclassification using Cox proportional hazards to compare the risk of severe coronavirus disease (COVID-19) (hospitalization & death) by ethnic group. RESULTS: Misclassification within PHS-EL was higher for all minority ethnic groups [12.5 to 69.1%] compared with the White Scottish majority [5.1%] and highest in the White Gypsy/Traveller group [69.1%]. Missingness in PHS-EL was highest among the White Other British group [39%] and lowest among the Pakistani group [17%]. PHS-EL data often underestimated severe COVID-19 risk compared with Census data. e.g. in the White Gypsy/Traveller group the Hazard Ratio (HR) was 1.68 [95% Confidence Intervals (CI): 1.03, 2.74] compared with the White Scottish majority using Census ethnicity data and 0.73 [95% CI: 0.10, 5.15] using PHS-EL data; and HR was 2.03 [95% CI: 1.20, 3.44] in the Census for the Bangladeshi group versus 1.45 [95% CI: 0.75, 2.78] in PHS-EL. CONCLUSIONS: Poor quality ethnicity coding in health records can bias estimates, thereby threatening monitoring and understanding ethnic inequalities in health.

Patient views on asthma diagnosis and how a clinical decision support system could help: A qualitative study.

INTRODUCTION: Making a diagnosis of asthma can be challenging for clinicians and patients. A clinical decision support system (CDSS) for use in primary care including a patient-facing mode, could change how information is shared between patients and healthcare professionals and improve the diagnostic process. METHODS: Participants diagnosed with asthma within the last 5 years were recruited from general practices across four UK regions. In-depth interviews were used to explore patient experiences relating to their asthma diagnosis and to understand how a CDSS could be used to improve the diagnostic process for patients. Interviews were audio recorded, transcribed verbatim and analysed using a thematic approach. RESULTS: Seventeen participants (12 female) undertook interviews, including 14 individuals and 3 parents of children with asthma. Being diagnosed with asthma was generally considered an uncertain process. Participants felt a lack of consultation time and poor communication affected their understanding of asthma and what to expect. Had the nature of asthma and the steps required to make a diagnosis been explained more clearly, patients felt their understanding and engagement in asthma self-management could have been improved. Participants considered that a CDSS could provide resources to support the diagnostic process, prompt dialogue, aid understanding and support shared decision-making. CONCLUSION: Undergoing an asthma diagnosis was uncertain for patients if their ideas and concerns were not addressed by clinicians and were influenced by a lack of consultation time and limitations in communication. An asthma diagnosis CDSS could provide structure and an interface to prompt dialogue, provide visuals about asthma to aid understanding and encourage patient involvement. PATIENT AND PUBLIC CONTRIBUTION: Prespecified semistructured interview topic guides (young person and adult versions) were developed by the research team and piloted with members of the Asthma UK Centre for Applied Research Patient and Public Involvement (PPI) group. Findings were regularly discussed within the research group and with PPI colleagues to aid the interpretation of data.

A clinical review of long-COVID with a focus on the respiratory system.

PURPOSE OF REVIEW: Persistence of symptoms after acute coronavirus disease 2019 (COVID-19), often described as long- COVID, is common and debilitating. In this article, we review the epidemiology, clinical features, and research priorities for long-COVID focusing on the respiratory system. RECENT FINDINGS: Breathlessness, cough and chest pain were the most commonly reported respiratory symptoms associated with long-COVID. In hospitalised patients, abnormalities on lung function testing or chest imaging were observed less commonly at 12 months compared to six months since discharge. Clinical assessment of patients with persisting symptoms after acute COVID-19 requires a comprehensive evaluation to exclude other possible causes for symptoms. With no robust current evidence for interventions to treat long-COVID respiratory symptoms, symptomatic treatment, supported self-management and pulmonary rehabilitation should be considered to help individuals with respiratory symptoms associated with long-COVID. SUMMARY: Long-COVID is a debilitating syndrome that often includes persisting respiratory symptoms and to a lesser degree, abnormalities in lung physiology or imaging. Respiratory features of long-COVID may reduce over time, yet resolution is not seen in all cases. Future research is needed to understand the natural history of long-COVID, identify factors associated with spontaneous improvement/persistence, investigate mechanisms for persisting symptoms, and test interventions to prevent and treat long-COVID.

Systematic meta-review of supported self-management for asthma: a healthcare perspective.

BACKGROUND: Supported self-management has been recommended by asthma guidelines for three decades; improving current suboptimal implementation will require commitment from professionals, patients and healthcare organisations. The Practical Systematic Review of Self-Management Support (PRISMS) meta-review and Reducing Care Utilisation through Self-management Interventions (RECURSIVE) health economic review were commissioned to provide a systematic overview of supported self-management to inform implementation. We sought to investigate if supported asthma self-management reduces use of healthcare resources and improves asthma control; for which target groups it works; and which components and contextual factors contribute to effectiveness. Finally, we investigated the costs to healthcare services of providing supported self-management. METHODS: We undertook a meta-review (systematic overview) of systematic reviews updated with randomised controlled trials (RCTs) published since the review search dates, and health economic meta-analysis of RCTs. Twelve electronic databases were searched in 2012 (updated in 2015; pre-publication update January 2017) for systematic reviews reporting RCTs (and update RCTs) evaluating supported asthma self-management. We assessed the quality of included studies and undertook a meta-analysis and narrative synthesis. RESULTS: A total of 27 systematic reviews (n = 244 RCTs) and 13 update RCTs revealed that supported self-management can reduce hospitalisations, accident and emergency attendances and unscheduled consultations, and improve markers of control and quality of life for people with asthma across a range of cultural, demographic and healthcare settings. Core components are patient education, provision of an action plan and regular professional review. Self-management is most effective when delivered in the context of proactive long-term condition management. The total cost (n = 24 RCTs) of providing self-management support is offset by a reduction in hospitalisations and accident and emergency visits (standard mean difference 0.13, 95% confidence interval -0.09 to 0.34). CONCLUSIONS: Evidence from a total of 270 RCTs confirms that supported self-management for asthma can reduce unscheduled care and improve asthma control, can be delivered effectively for diverse demographic and cultural groups, is applicable in a broad range of clinical settings, and does not significantly increase total healthcare costs. Informed by this comprehensive synthesis of the literature, clinicians, patient-interest groups, policy-makers and providers of healthcare services should prioritise provision of supported self-management for people with asthma as a core component of routine care. SYSTEMATIC REVIEW REGISTRATION: RECURSIVE: PROSPERO CRD42012002694 ; PRISMS: PROSPERO does not register meta-reviews.

Telehealth Interventions to Support Self-Management of Long-Term Conditions: A Systematic Metareview of Diabetes, Heart Failure, Asthma, Chronic Obstructive Pulmonary Disease, and Cancer.

BACKGROUND: Self-management support is one mechanism by which telehealth interventions have been proposed to facilitate management of long-term conditions. OBJECTIVE: The objectives of this metareview were to (1) assess the impact of telehealth interventions to support self-management on disease control and health care utilization, and (2) identify components of telehealth support and their impact on disease control and the process of self-management. Our goal was to synthesise evidence for telehealth-supported self-management of diabetes (types 1 and 2), heart failure, asthma, chronic obstructive pulmonary disease (COPD) and cancer to identify components of effective self-management support. METHODS: We performed a metareview (a systematic review of systematic reviews) of randomized controlled trials (RCTs) of telehealth interventions to support self-management in 6 exemplar long-term conditions. We searched 7 databases for reviews published from January 2000 to May 2016 and screened identified studies against eligibility criteria. We weighted reviews by quality (revised A Measurement Tool to Assess Systematic Reviews), size, and relevance. We then combined our results in a narrative synthesis and using harvest plots. RESULTS: We included 53 systematic reviews, comprising 232 unique RCTs. Reviews concerned diabetes (type 1: n=6; type 2, n=11; mixed, n=19), heart failure (n=9), asthma (n=8), COPD (n=8), and cancer (n=3). Findings varied between and within disease areas. The highest-weighted reviews showed that blood glucose telemonitoring with feedback and some educational and lifestyle interventions improved glycemic control in type 2, but not type 1, diabetes, and that telemonitoring and telephone interventions reduced mortality and hospital admissions in heart failure, but these findings were not consistent in all reviews. Results for the other conditions were mixed, although no reviews showed evidence of harm. Analysis of the mediating role of self-management, and of components of successful interventions, was limited and inconclusive. More intensive and multifaceted interventions were associated with greater improvements in diabetes, heart failure, and asthma. CONCLUSIONS: While telehealth-mediated self-management was not consistently superior to usual care, none of the reviews reported any negative effects, suggesting that telehealth is a safe option for delivery of self-management support, particularly in conditions such as heart failure and type 2 diabetes, where the evidence base is more developed. Larger-scale trials of telehealth-supported self-management, based on explicit self-management theory, are needed before the extent to which telehealth technologies may be harnessed to support self-management can be established.

Risk of winter hospitalisation and death from acute respiratory infections in Scotland: national retrospective cohort study.

OBJECTIVES: We undertook a national analysis to characterise and identify risk factors for acute respiratory infections (ARIs) resulting in hospitalisation during the winter period in Scotland. DESIGN: A population-based retrospective cohort analysis. SETTING: Scotland. PARTICIPANTS: The study involved 5.4 million residents in Scotland. MAIN OUTCOME MEASURES: Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the association between risk factors and ARI hospitalisation. RESULTS: Between 1 September 2022 and 31 January 2023, there were 22,284 (10.9% of 203,549 with any emergency hospitalisation) ARI hospitalisations (1759 in children and 20,525 in adults) in Scotland. Compared with the reference group of children aged 6-17 years, the risk of ARI hospitalisation was higher in children aged 3-5 years (aHR = 4.55; 95% CI: 4.11-5.04). Compared with those aged 25-29 years, the risk of ARI hospitalisation was highest among the oldest adults aged ≥80 years (aHR = 7.86; 95% CI: 7.06-8.76). Adults from more deprived areas (most deprived vs. least deprived, aHR = 1.64; 95% CI: 1.57-1.72), with existing health conditions (≥5 vs. 0 health conditions, aHR = 4.84; 95% CI: 4.53-5.18) or with history of all-cause emergency admissions (≥6 vs. 0 previous emergency admissions, aHR = 7.53; 95% CI: 5.48-10.35) were at a higher risk of ARI hospitalisations. The risk increased by the number of existing health conditions and previous emergency admission. Similar associations were seen in children. CONCLUSIONS: Younger children, older adults, those from more deprived backgrounds and individuals with greater numbers of pre-existing conditions and previous emergency admission were at increased risk for winter hospitalisations for ARI.

Prevalence and risk factors for long COVID among adults in Scotland using electronic health records: a national, retrospective, observational cohort study.

Background: Long COVID is a debilitating multisystem condition. The objective of this study was to estimate the prevalence of long COVID in the adult population of Scotland, and to identify risk factors associated with its development. Methods: In this national, retrospective, observational cohort study, we analysed electronic health records (EHRs) for all adults (≥18 years) registered with a general medical practice and resident in Scotland between March 1, 2020, and October 26, 2022 (98-99% of the population). We linked data from primary care, secondary care, laboratory testing and prescribing. Four outcome measures were used to identify long COVID: clinical codes, free text in primary care records, free text on sick notes, and a novel operational definition. The operational definition was developed using Poisson regression to identify clinical encounters indicative of long COVID from a sample of negative and positive COVID-19 cases matched on time-varying propensity to test positive for SARS-CoV-2. Possible risk factors for long COVID were identified by stratifying descriptive statistics by long COVID status. Findings: Of 4,676,390 participants, 81,219 (1.7%) were identified as having long COVID. Clinical codes identified the fewest cases (n = 1,092, 0.02%), followed by free text (n = 8,368, 0.2%), sick notes (n = 14,469, 0.3%), and the operational definition (n = 64,193, 1.4%). There was limited overlap in cases identified by the measures; however, temporal trends and patient characteristics were consistent across measures. Compared with the general population, a higher proportion of people with long COVID were female (65.1% versus 50.4%), aged 38-67 (63.7% versus 48.9%), overweight or obese (45.7% versus 29.4%), had one or more comorbidities (52.7% versus 36.0%), were immunosuppressed (6.9% versus 3.2%), shielding (7.9% versus 3.4%), or hospitalised within 28 days of testing positive (8.8% versus 3.3%%), and had tested positive before Omicron became the dominant variant (44.9% versus 35.9%). The operational definition identified long COVID cases with combinations of clinical encounters (from four symptoms, six investigation types, and seven management strategies) recorded in EHRs within 4-26 weeks of a positive SARS-CoV-2 test. These combinations were significantly (p < 0.0001) more prevalent in positive COVID-19 patients than in matched negative controls. In a case-crossover analysis, 16.4% of those identified by the operational definition had similar healthcare patterns recorded before testing positive. Interpretation: The prevalence of long COVID presenting in general practice was estimated to be 0.02-1.7%, depending on the measure used. Due to challenges in diagnosing long COVID and inconsistent recording of information in EHRs, the true prevalence of long COVID is likely to be higher. The operational definition provided a novel approach but relied on a restricted set of symptoms and may misclassify individuals with pre-existing health conditions. Further research is needed to refine and validate this approach. Funding: Chief Scientist Office (Scotland), Medical Research Council, and BREATHE.

Association between antibody responses post-vaccination and severe COVID-19 outcomes in Scotland.

Several population-level studies have described individual clinical risk factors associated with suboptimal antibody responses following COVID-19 vaccination, but none have examined multimorbidity. Others have shown that suboptimal post-vaccination responses offer reduced protection to subsequent SARS-CoV-2 infection; however, the level of protection from COVID-19 hospitalisation/death remains unconfirmed. We use national Scottish datasets to investigate the association between multimorbidity and testing antibody-negative, examining the correlation between antibody levels and subsequent COVID-19 hospitalisation/death among double-vaccinated individuals. We found that individuals with multimorbidity ( ≥ five conditions) were more likely to test antibody-negative post-vaccination and 13.37 [6.05-29.53] times more likely to be hospitalised/die from COVID-19 than individuals without conditions. We also show a dose-dependent association between post-vaccination antibody levels and COVID-19 hospitalisation or death, with those with undetectable antibody levels at a significantly higher risk (HR 9.21 [95% CI 4.63-18.29]) of these serious outcomes compared to those with high antibody levels.

Evaluation of remote digital postoperative wound monitoring in routine surgical practice.

Remote digital postoperative wound monitoring provides an opportunity to strengthen postoperative community care and minimise the burden of surgical-site infection (SSI). This study aimed to pilot a remote digital postoperative wound monitoring service and evaluate the readiness for implementation in routine clinical practice. This was a single-arm pilot implementational study of remote digital postoperative wound monitoring across two tertiary care hospitals in the UK (IDEAL stage 2b, clinicaltrials.gov: NCT05069103). Adults undergoing abdominal surgery were recruited and received a smartphone-delivered wound assessment tool for 30-days postoperatively. Patients received 30-day postoperative follow-up, including the Telehealth Usability Questionnaire (TUQ). A thematic mixed-methods approach was used, according to the WHO framework for monitoring and evaluating digital health interventions. 200 patients were enroled, of whom 115 (57.5%) underwent emergency surgical procedures. Overall, the 30-day SSI rate was 16.5% (n = 33/200), with 72.7% (n = 24) diagnosed post-discharge. Usage of the intervention was 83.0% (n = 166/200), with subsequently 74.1% (n = 123/166) TUQ completion. There were no issues reported with feasibility of the technology, with the reliability (3.87, 95% CI: 3.73-4.00) and quality of the interface rated highly (4.18, 95%: 4.06-4.30). Patient acceptance was similarly high with regards to ease of use (4.51, 95% CI: 4.41-4.62), satisfaction (4.27, 95% CI: 4.13-4.41), and usefulness (4.07, 95% CI: 3.92-4.23). Despite the desire for more frequent and personalised interactions, the majority viewed the intervention as providing meaningful benefit over routine postoperative care. Remote digital postoperative wound monitoring successfully demonstrated readiness for implementation with regards to the technology, usability, and healthcare process improvement.

Deriving and validating an asthma diagnosis prediction model for children and young people in primary care.

Introduction: Accurately diagnosing asthma can be challenging. We aimed to derive and validate a prediction model to support primary care clinicians assess the probability of an asthma diagnosis in children and young people. Methods: The derivation dataset was created from the Avon Longitudinal Study of Parents and Children (ALSPAC) linked to electronic health records. Participants with at least three inhaled corticosteroid prescriptions in 12-months and a coded asthma diagnosis were designated as having asthma. Demographics, symptoms, past medical/family history, exposures, investigations, and prescriptions were considered as candidate predictors. Potential candidate predictors were included if data were available in ≥60% of participants. Multiple imputation was used to handle remaining missing data. The prediction model was derived using logistic regression. Internal validation was completed using bootstrap re-sampling. External validation was conducted using health records from the Optimum Patient Care Research Database (OPCRD). Results: Predictors included in the final model were wheeze, cough, breathlessness, hay-fever, eczema, food allergy, social class, maternal asthma, childhood exposure to cigarette smoke, prescription of a short acting beta agonist and the past recording of lung function/reversibility testing. In the derivation dataset, which comprised 11,972 participants aged <25 years (49% female, 8% asthma), model performance as indicated by the C-statistic and calibration slope was 0.86, 95% confidence interval (CI) 0.85-0.87 and 1.00, 95% CI 0.95-1.05 respectively. In the external validation dataset, which included 2,670 participants aged <25 years (50% female, 10% asthma), the C-statistic was 0.85, 95% CI 0.83-0.88, and calibration slope 1.22, 95% CI 1.09-1.35. Conclusions: We derived and validated a prediction model for clinicians to calculate the probability of asthma diagnosis for a child or young person up to 25 years of age presenting to primary care. Following further evaluation of clinical effectiveness, the prediction model could be implemented as a decision support software.

Ethnic inequalities in positive SARS-CoV-2 tests, infection prognosis, COVID-19 hospitalisations and deaths: analysis of 2 years of a record linked national cohort study in Scotland.

BACKGROUND: This study aims to estimate ethnic inequalities in risk for positive SARS-CoV-2 tests, COVID-19 hospitalisations and deaths over time in Scotland. METHODS: We conducted a population-based cohort study where the 2011 Scottish Census was linked to health records. We included all individuals ≥ 16 years living in Scotland on 1 March 2020. The study period was from 1 March 2020 to 17 April 2022. Self-reported ethnic group was taken from the census and Cox proportional hazard models estimated HRs for positive SARS-CoV-2 tests, hospitalisations and deaths, adjusted for age, sex and health board. We also conducted separate analyses for each of the four waves of COVID-19 to assess changes in risk over time. FINDINGS: Of the 4 358 339 individuals analysed, 1 093 234 positive SARS-CoV-2 tests, 37 437 hospitalisations and 14 158 deaths occurred. The risk of COVID-19 hospitalisation or death among ethnic minority groups was often higher for White Gypsy/Traveller (HR 2.21, 95% CI (1.61 to 3.06)) and Pakistani 2.09 (1.90 to 2.29) groups compared with the white Scottish group. The risk of COVID-19 hospitalisation or death following confirmed positive SARS-CoV-2 test was particularly higher for White Gypsy/Traveller 2.55 (1.81-3.58), Pakistani 1.75 (1.59-1.73) and African 1.61 (1.28-2.03) individuals relative to white Scottish individuals. However, the risk of COVID-19-related death following hospitalisation did not differ. The risk of COVID-19 outcomes for ethnic minority groups was higher in the first three waves compared with the fourth wave. INTERPRETATION: Most ethnic minority groups were at increased risk of adverse COVID-19 outcomes in Scotland, especially White Gypsy/Traveller and Pakistani groups. Ethnic inequalities persisted following community infection but not following hospitalisation, suggesting differences in hospital treatment did not substantially contribute to ethnic inequalities.

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls.

Background: The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods: We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings: We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01-1.03), male (1.54, 1.16-2.04), neither obese nor severely obese (1.82, 1.06-3.13 and 4.19, 2.14-8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09-2.22) or cardiovascular disease (1.33, 1.00-1.79), and shorter hospital admission (1.01 per day, 1.00-1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation: Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding: PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care.COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders.

Characteristics and risk factors for post-COVID-19 breathlessness after hospitalisation for COVID-19.

Background: Persistence of respiratory symptoms, particularly breathlessness, after acute coronavirus disease 2019 (COVID-19) infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation. Methods: PHOSP-COVID is a multicentre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a follow-up visit. Breathlessness was measured by a numeric rating scale of 0-10. We defined post-COVID-19 breathlessness as an increase in score of ≥1 compared to the pre-COVID-19 level. Multivariable logistic regression was used to identify risk factors and to develop a prediction model for post-COVID-19 breathlessness. Results: We included 1226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median 5 months after discharge, 50% reported post-COVID-19 breathlessness. Risk factors for post-COVID-19 breathlessness were socioeconomic deprivation (adjusted OR 1.67, 95% CI 1.14-2.44), pre-existing depression/anxiety (adjusted OR 1.58, 95% CI 1.06-2.35), female sex (adjusted OR 1.56, 95% CI 1.21-2.00) and admission duration (adjusted OR 1.01, 95% CI 1.00-1.02). Black ethnicity (adjusted OR 0.56, 95% CI 0.35-0.89) and older age groups (adjusted OR 0.31, 95% CI 0.14-0.66) were less likely to report post-COVID-19 breathlessness. Post-COVID-19 breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. The prediction model had fair discrimination (concordance statistic 0.66, 95% CI 0.63-0.69) and good calibration (calibration slope 1.00, 95% CI 0.80-1.21). Conclusions: Post-COVID-19 breathlessness was commonly reported in this national cohort of patients hospitalised for COVID-19 and is likely to be a multifactorial problem with physical and emotional components.

Symptoms and signs of long COVID: A rapid review and meta-analysis.

Background: Long COVID is defined as symptoms and signs related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are present at least four weeks following acute infection. These symptoms and signs are poorly characterised but may be associated with significant morbidity. We sought to synthesise the evidence on their incidence to guide future research, policy and practice. Methods: We searched Medline and Embase for longitudinal cohort studies from January 2020 to July 2021 that investigated adults with long COVID at least four weeks after acute infection. Risk of bias was assessed using the Joanna Briggs Institute checklist for cohort studies. Random-effects meta-analyses were performed with subgroup analysis by follow-up time (4-12 vs more than 12 weeks). Results: 19 studies were included, 13 of which included patients hospitalised with COVID-19. The total sample size was 10 643 and the follow-up time ranged from 30 to 340 days. Risk of bias was assessed as high in one study, moderate in two studies and low in the remaining 16 studies. The most common symptoms and signs seen at any time point in long COVID were fatigue (37%; 95% confidence interval (CI) = 23-55), dyspnoea (21%; 95% CI = 14-30), olfactory dysfunction (17%; 95% CI = 9-29), myalgia (12%; 95% CI = 5-25), cough (11%; 95% CI = 6-20) and gustatory dysfunction (10%; 95% CI = 7-17). High heterogeneity was seen for all meta-analyses and the presence of some funnel plot asymmetry may indicate reporting bias. No effect of follow-up time was found for any symptom or sign included in the subgroup analysis. Conclusions: We have summarised evidence from longitudinal cohort studies on the most common symptoms and signs associated with long COVID. High heterogeneity seen in the meta-analysis means pooled incidence estimates should be interpreted with caution. This heterogeneity may be attributable to studies including patients from different health care settings and countries.

Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms.

Emerging evidence has shown that COVID-19 survivors could suffer from persistent symptoms. However, it remains unclear whether these symptoms persist over the longer term. This study aimed to systematically synthesise evidence on post-COVID symptoms persisting for at least 12 months. We searched PubMed and Embase for papers reporting at least one-year follow-up results of COVID-19 survivors published by 6 November 2021. Random-effects meta-analyses were conducted to estimate pooled prevalence of specific post-COVID symptoms. Eighteen papers that reported one-year follow-up data from 8591 COVID-19 survivors were included. Fatigue/weakness (28%, 95% CI: 18-39), dyspnoea (18%, 95% CI: 13-24), arthromyalgia (26%, 95% CI: 8-44), depression (23%, 95% CI: 12-34), anxiety (22%, 95% CI: 15-29), memory loss (19%, 95% CI: 7-31), concentration difficulties (18%, 95% CI: 2-35), and insomnia (12%, 95% CI: 7-17) were the most prevalent symptoms at one-year follow-up. Existing evidence suggested that female patients and those with more severe initial illness were more likely to suffer from the sequelae after one year. This study demonstrated that a sizeable proportion of COVID-19 survivors still experience residual symptoms involving various body systems one year later. There is an urgent need for elucidating the pathophysiologic mechanisms and developing and testing targeted interventions for long-COVID patients.

Deriving and validating a risk prediction model for long COVID-19: protocol for an observational cohort study using linked Scottish data.

INTRODUCTION: COVID-19 is commonly experienced as an acute illness, yet some people continue to have symptoms that persist for weeks, or months (commonly referred to as 'long-COVID'). It remains unclear which patients are at highest risk of developing long-COVID. In this protocol, we describe plans to develop a prediction model to identify individuals at risk of developing long-COVID. METHODS AND ANALYSIS: We will use the national Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, a population-level linked dataset of routine electronic healthcare data from 5.4 million individuals in Scotland. We will identify potential indicators for long-COVID by identifying patterns in primary care data linked to information from out-of-hours general practitioner encounters, accident and emergency visits, hospital admissions, outpatient visits, medication prescribing/dispensing and mortality. We will investigate the potential indicators of long-COVID by performing a matched analysis between those with a positive reverse transcriptase PCR (RT-PCR) test for SARS-CoV-2 infection and two control groups: (1) individuals with at least one negative RT-PCR test and never tested positive; (2) the general population (everyone who did not test positive) of Scotland. Cluster analysis will then be used to determine the final definition of the outcome measure for long-COVID. We will then derive, internally and externally validate a prediction model to identify the epidemiological risk factors associated with long-COVID. ETHICS AND DISSEMINATION: The EAVE II study has obtained approvals from the Research Ethics Committee (reference: 12/SS/0201), and the Public Benefit and Privacy Panel for Health and Social Care (reference: 1920-0279). Study findings will be published in peer-reviewed journals and presented at conferences. Understanding the predictors for long-COVID and identifying the patient groups at greatest risk of persisting symptoms will inform future treatments and preventative strategies for long-COVID.

Deriving a Standardised Recommended Respiratory Disease Codelist Repository for Future Research.

BACKGROUND: Electronic health record (EHR) databases provide rich, longitudinal data on interactions with healthcare providers and can be used to advance research into respiratory conditions. However, since these data are primarily collected to support health care delivery, clinical coding can be inconsistent, resulting in inherent challenges in using these data for research purposes. METHODS: We systematically searched existing international literature and UK code repositories to find respiratory disease codelists for asthma from January 2018, and chronic obstructive pulmonary disease and respiratory tract infections from January 2020, based on prior searches. Medline searches using key terms provided in article lists. Full-text articles, supplementary files, and reference lists were examined for codelists, and codelists repositories were searched. A reproducible methodology for codelists creation was developed with recommended lists for each disease created based on multidisciplinary expert opinion and previously published literature. RESULTS: Medline searches returned 1126 asthma articles, 70 COPD articles, and 90 respiratory infection articles, with 3%, 22% and 5% including codelists, respectively. Repository searching returned 12 asthma, 23 COPD, and 64 respiratory infection codelists. We have systematically compiled respiratory disease codelists and from these derived recommended lists for use by researchers to find the most up-to-date and relevant respiratory disease codelists that can be tailored to individual research questions. CONCLUSION: Few published papers include codelists, and where published diverse codelists were used, even when answering similar research questions. Whilst some advances have been made, greater consistency and transparency across studies using routine data to study respiratory diseases are needed.

Prevalence, risk factors and treatments for post-COVID-19 breathlessness: a systematic review and meta-analysis.

Persistent breathlessness >28 days after acute COVID-19 infection has been identified as a highly debilitating post-COVID symptom. However, the prevalence, risk factors, mechanisms and treatments for post-COVID breathlessness remain poorly understood. We systematically searched PubMed and Embase for relevant studies published from 1 January 2020 to 1 November 2021 (PROSPERO registration number: CRD42021285733) and included 119 eligible papers. Random-effects meta-analysis of 42 872 patients with COVID-19 reported in 102 papers found an overall prevalence of post-COVID breathlessness of 26% (95% CI 23-29) when measuring the presence/absence of the symptom, and 41% (95% CI 34-48) when using Medical Research Council (MRC)/modified MRC dyspnoea scale. The pooled prevalence decreased significantly from 1-6 months to 7-12 months post-infection. Post-COVID breathlessness was more common in those with severe/critical acute infection, those who were hospitalised and females, and was less likely to be reported by patients in Asia than those in Europe or North America. Multiple pathophysiological mechanisms have been proposed (including deconditioning, restrictive/obstructive airflow limitation, systemic inflammation, impaired mental health), but the body of evidence remains inconclusive. Seven cohort studies and one randomised controlled trial suggested rehabilitation exercises may reduce post-COVID breathlessness. There is an urgent need for mechanistic research and development of interventions for the prevention and treatment of post-COVID breathlessness.

Diagnostic accuracy of FeNO [fractional exhaled nitric oxide] and asthma symptoms increased when evaluated with a superior reference standard.

OBJECTIVES: The objective of the study is to determine the impact of changing reference standards (RS), namely spirometry vs. whole-body plethysmography (WBP), on estimation of the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) and clinical signs and symptoms (CSS) as index tests regarding asthma diagnosis. STUDY DESIGN AND SETTING: This was a diagnostic study conducted in 393 patients attending a private practice of pneumologists with complaints suspicious of asthma. First, the index tests were compared with the diagnostic results of spirometry in terms of forced expiratory volume in the first second (FEV1) responsiveness. Second, the index tests were compared with the results of WBP in terms of specific airway resistance and FEV1 responsiveness. Areas under the curve (AUC) were compared with a generalized estimating equation approach based on binary logistic regression. RESULTS: FeNO values and CSS 'wheezing' and 'allergic rhinitis' showed higher specificities (P < 0.001) and sensitivities (not significant) when evaluated with WBP; also, Youden indices increased in these CSS (P < 0.05). AUC of FeNO in combination with 'wheezing' and 'allergic rhinitis' when WBP was used as RS (AUC = 0.724; 95% confidence interval 0.672 to 0.776) was higher compared with spirometry as RS (AUC = 0.654; 95% confidence interval 0.585 to 0.722) (P < 0.001). CONCLUSION: In case of asthma, superior RS led to more favorable assessment of index tests. FeNO measurement might have been underestimated in some previous studies.