Identification of key opportunities for optimising the management of high-risk COPD patients in the UK using the CONQUEST quality standards: an observational longitudinal study.

Background: This study compared management of high-risk COPD patients in the UK to national and international management recommendations and quality standards, including the COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST). The primary comparison was in 2019, but trends from 2000 to 2019 were also examined. Methods: Patients identified in the Optimum Patient Care Research Database were categorised as newly diagnosed (≤12 months after diagnosis), already diagnosed, and potential COPD (smokers having exacerbation-like events). High-risk patients had a history of ≥2 moderate or ≥1 severe exacerbations in the previous 12 months. Findings: For diagnosed patients, the median time between diagnosis and first meeting the high-risk criteria was 617 days (Q1-Q3: 3246). The use of spirometry for diagnosis increased dramatically after 2004 before plateauing and falling in recent years. In 2019, 41% (95% CI 39-44%; n = 550/1343) of newly diagnosed patients had no record of spirometry in the previous year, and 45% (95% CI 43-48%; n = 352/783) had no record of a COPD medication review within 6 months of treatment initiation or change. In 2019, 39% (n = 6893/17,858) of already diagnosed patients had no consideration of exacerbation rates, 46% (95% CI 45-47%; n = 4942/10,725) were not offered or referred for pulmonary rehabilitation, and 41% (95% CI 40-42%; n = 3026/7361) had not had a COPD review within 6 weeks of respiratory hospitalization. Interpretation: Opportunities for early diagnosis of COPD patients at high risk of exacerbations are being missed. Newly and already diagnosed patients at high-risk are not being assessed or treated promptly. There is substantial scope to improve the assessment and treatment optimisation of these patients. Funding: This study is conducted by the Observational & Pragmatic Research International Ltd and was co-funded by Optimum Patient Care and AstraZeneca. No funding was received by the Observational & Pragmatic Research Institute Pte Ltd (OPRI) for its contribution.

Comparison of COPD primary care in England, Scotland, Wales, and Northern Ireland.

Currently the National Asthma and COPD audit programme (NACAP) only undertakes audit of COPD primary care in Wales due to its near complete data coverage. We aimed to determine if the quality of COPD primary care in the other UK nations is comparable with Wales. We found that English, Scottish, and Northern Irish practices were significantly worse than Welsh practices at recording coded lung function parameters used in COPD diagnosis (ORs: 0.51 [0.43-0.59], 0.29 [0.23-0.36], 0.42 [0.31-0.58], respectively) and referring appropriate patients for pulmonary rehabilitation (ORs: 0.10 [0.09-0.11], 0.12 [0.11-0.14], 0.22 [0.19-0.25], respectively). Completing national audits of primary care in Wales only may have led to improvements in care, or at least improvements in the recording of care in Wales that are not occurring elsewhere in the UK. This highlights the potential importance of audit in improving care quality and accurate recording of that care.

Risk Predictors and Symptom Features of Long COVID Within a Broad Primary Care Patient Population Including Both Tested and Untested Patients.

INTRODUCTION: Symptoms may persist after the initial phases of COVID-19 infection, a phenomenon termed long COVID. Current knowledge on long COVID has been mostly derived from test-confirmed and hospitalized COVID-19 patients. Data are required on the burden and predictors of long COVID in a broader patient group, which includes both tested and untested COVID-19 patients in primary care. METHODS: This is an observational study using data from Platform C19, a quality improvement program-derived research database linking primary care electronic health record data (EHR) with patient-reported questionnaire information. Participating general practices invited consenting patients aged 18-85 to complete an online questionnaire since 7th August 2020. COVID-19 self-diagnosis, clinician-diagnosis, testing, and the presence and duration of symptoms were assessed via the questionnaire. Patients were considered present with long COVID if they reported symptoms lasting ≥4 weeks. EHR and questionnaire data up till 22nd January 2021 were extracted for analysis. Multivariable regression analyses were conducted comparing demographics, clinical characteristics, and presence of symptoms between patients with long COVID and patients with shorter symptom duration. RESULTS: Long COVID was present in 310/3151 (9.8%) patients with self-diagnosed, clinician-diagnosed, or test-confirmed COVID-19. Only 106/310 (34.2%) long COVID patients had test-confirmed COVID-19. Risk predictors of long COVID were age ≥40 years (adjusted Odds Ratio [AdjOR]=1.49 [1.05-2.17]), female sex (adjOR=1.37 [1.02-1.85]), frailty (adjOR=2.39 [1.29-4.27]), visit to A&E (adjOR=4.28 [2.31-7.78]), and hospital admission for COVID-19 symptoms (adjOR=3.22 [1.77-5.79]). Aches and pain (adjOR=1.70 [1.21-2.39]), appetite loss (adjOR=3.15 [1.78-5.92]), confusion and disorientation (adjOR=2.17 [1.57-2.99]), diarrhea (adjOR=1.4 [1.03-1.89]), and persistent dry cough (adjOR=2.77 [1.94-3.98]) were symptom features statistically more common in long COVID. CONCLUSION: This study reports the factors and symptom features predicting long COVID in a broad primary care population, including both test-confirmed and the previously missed group of COVID-19 patients.

Predictors of pulmonary rehabilitation completion in the UK.

INTRODUCTION: Pulmonary rehabilitation has been shown to improve dyspnoea, fatigue, quality of life and exercise capacity in individuals with chronic obstructive pulmonary disease (COPD). Our aim was to determine the characteristics of people with COPD associated with completion of pulmonary rehabilitation. METHODS: This was a cross-sectional analysis of 7060 people with COPD enrolled in pulmonary rehabilitation between January 1, 2017 and March 31, 2017. Data were from a UK national audit of COPD care. Factors associated with pulmonary rehabilitation completion were determined using mixed effects logistic regression with a random intercept for pulmonary rehabilitation service. Factors chosen for assessment based on clinical judgement and data availability were age, sex, country, socioeconomic status, body mass index, referral location, programme type, start within 90 days, smoking status, oxygen therapy, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, Medical Research Council (MRC) dyspnoea grade, any exercise test and any health status questionnaire. RESULTS: 4635 (66%) people with COPD completed a pulmonary rehabilitation programme. People that were aged ≥60 years, resident in Wales, referred within 90 days, an ex- or never-smoker, received an exercise test, or received a health status questionnaire had significantly greater odds of completing pulmonary rehabilitation. People that were in the most deprived quintile, underweight or very severely obese, enrolled in a rolling rather than a cohort programme, had a higher GOLD stage and had a higher MRC grade had significantly lower odds of completing pulmonary rehabilitation. CONCLUSIONS: People with COPD were more likely to complete pulmonary rehabilitation when best practice guidelines were followed. People with more severe COPD symptoms and those enrolled in rolling rather than cohort programmes were less likely to complete pulmonary rehabilitation. Referring people with COPD in the earlier stages of disease, ensuring programmes follow best practice guidelines and favouring cohort over rolling programmes could improve rates of pulmonary rehabilitation completion.

Predictors of Referral to Pulmonary Rehabilitation from UK Primary Care.

Background: A large proportion of people with COPD are not referred to pulmonary rehabilitation (PR) despite its proven benefits. No previous studies have examined predictors of referral to PR. Objective: To determine the characteristics of people with COPD associated with referral to PR. Methods: Cross-sectional analysis of a primary care cohort of 82,696 Welsh people with COPD generated as part of a UK national audit of COPD care. Data represent care received by patients as of 31/03/2017. Referral to PR was defined as any code in the patient record indicating referral to PR in the last 3 years. Potential predictors of referral to PR were chosen based on clinical judgement and data availability. Independent predictors of PR referral were determined using backward stepwise mixed-effects logistic regression with a random effect for practice. Variables assessed were: age, gender, deprivation, MRC recorded in past year, MRC grade, smoking status recorded in past year, smoking status, number of exacerbations in past year, inhaled therapy prescription, influenza vaccination, and comorbidities of diabetes, hypertension, coronary heart disease, stroke, heart failure, lung cancer, asthma, bronchiectasis, depression, anxiety, severe mental illness, osteoporosis, and painful condition. Results: A total of 13,297 people (16%) with COPD were referred from primary care for PR. Patients with a comorbidity of bronchiectasis or depression, MRC recorded in the last year, higher MRC grade, more exacerbations in the last year, a greater level of inhaled therapy, an influenza vaccination, or were an ex-smoker had significantly higher odds of referral to PR. Patients that were older, female, more deprived, or had a comorbidity of diabetes, asthma, or painful condition had significantly lower odds of referral to PR. Conclusion: Generally appropriate patients are being prioritised for PR referral; however, it is concerning that women, current smokers, and more deprived patients appear to have lower odds of referral.

Development of an integrated rehabilitation pathway for individuals recovering from COVID-19 in the community.

OBJECTIVE: COVID-19 is a multisystem illness that has considerable long-term physical, psychological, cognitive, social and vocational sequelae in survivors. Given the scale of this burden and lockdown measures in most countries, there is a need for an integrated rehabilitation pathway using a tele-medicine approach to screen and manage these sequelae in a systematic and efficient way. METHODS: A multidisciplinary team of professionals in the UK developed a comprehensive pragmatic telephone screening tool, the COVID-19 Yorkshire Rehabilitation Screen (C19-YRS), and an integrated rehabilitation pathway, which spans the acute hospital trust, community trust and primary care service within the National Health Service (NHS) service model. RESULTS: The C19-YRS telephone screening tool, developed previously, was used to screen symptoms and grade their severity. Referral criteria thresholds were applied to the output of C19-YRS to inform the decision-making process in the rehabilitation pathway. A dedicated multidisciplinary COVID-19 rehabilitation team is the core troubleshooting forum for managing complex cases with needs spanning multiple domains of the health condition. CONCLUSION: The authors recommend that health services dealing with the COVID-19 pandemic adopt a comprehensive telephone screening system and an integrated rehabilitation pathway to manage the large number of survivors in a timely and effective manner and to enable the provision of targeted interventions.

MYC Deregulation in Primary Human Cancers.

MYC regulates a complex biological program by transcriptionally activating and repressing its numerous target genes. As such, MYC is a master regulator of many processes, including cell cycle entry, ribosome biogenesis, and metabolism. In cancer, the activity of the MYC transcriptional network is frequently deregulated, contributing to the initiation and maintenance of disease. Deregulation often leads to constitutive overexpression of MYC, which can be achieved through gross genetic abnormalities, including copy number alterations, chromosomal translocations, increased enhancer activity, or through aberrant signal transduction leading to increased MYC transcription or increased MYC mRNA and protein stability. Herein, we summarize the frequency and modes of MYC deregulation and describe both well-established and more recent findings in a variety of cancer types. Notably, these studies have highlighted that with an increased appreciation for the basic mechanisms deregulating MYC in cancer, new therapeutic vulnerabilities can be discovered and potentially exploited for the inhibition of this potent oncogene in cancer.