The Economic Potential of Smoking Cessation Interventions at the Point of Diagnosis of Non-Small Cell Lung Cancer.

OBJECTIVES: Stopping smoking has proven benefits in nearly all illnesses but the impact and health economic benefits of stopping smoking after a diagnosis of lung cancer are less well defined. We assessed the cost-effectiveness of smoking cessation (SC) services for patients with newly diagnosed lung cancer against current usual care, where patients are unlikely to receive SC service referral. METHODS: A health economic model was constructed in Excel. The modelled population comprised of patients with a new diagnosis of non-small cell lung cancer (NSCLC). Data from the LungCast data set (Clinical Trials Identifier NCT01192256) were used to estimate model inputs. A structured search of published literature identified inputs not represented in LungCast, including healthcare resource use and costs. Costs were estimated from a 2020/2021 UK National Health Service and Personal Social Services perspective. The model estimated the incremental quality-adjusted life-year (QALY) gained in patients with newly diagnosed NSCLC receiving targeted SC intervention than those receiving no intervention. Extensive one-way sensitivity analyses explored input and data set uncertainty. RESULTS: In the 5-year base case, the model estimated an incremental cost of £14 904 per QALY gained through SC intervention. Sensitivity analysis estimated an outcome range of between £9935 and £32 246 per QALY gained. The model was most sensitive to the estimates of relative quit rates and expected healthcare resource use. CONCLUSION: This exploratory analysis indicates that SC intervention for smokers with patients with newly diagnosed NSCLC should be a cost-effective use of UK National Health Service resources. Additional research with focused costing is needed to confirm this positioning.

The Noninvasive Ventilation Outcomes (NIVO) score: prediction of in-hospital mortality in exacerbations of COPD requiring assisted ventilation.

INTRODUCTION: Acute exacerbations of COPD (AECOPD) complicated by acute (acidaemic) hypercapnic respiratory failure (AHRF) requiring ventilation are common. When applied appropriately, ventilation substantially reduces mortality. Despite this, there is evidence of poor practice and prognostic pessimism. A clinical prediction tool could improve decision making regarding ventilation, but none is routinely used. METHODS: Consecutive patients admitted with AECOPD and AHRF treated with assisted ventilation (principally noninvasive ventilation) were identified in two hospitals serving differing populations. Known and potential prognostic indices were identified a priori. A prediction tool for in-hospital death was derived using multivariable regression analysis. Prospective, external validation was performed in a temporally separate, geographically diverse 10-centre study. The trial methodology adhered to TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) recommendations. RESULTS: Derivation cohort: n=489, in-hospital mortality 25.4%; validation cohort: n=733, in-hospital mortality 20.1%. Using six simple categorised variables (extended Medical Research Council Dyspnoea score 1-4/5a/5b, time from admission to acidaemia >12 h, pH <7.25, presence of atrial fibrillation, Glasgow coma scale ≤14 and chest radiograph consolidation), a simple scoring system with strong prediction of in-hospital mortality is achieved. The resultant Noninvasive Ventilation Outcomes (NIVO) score had area under the receiver operating curve of 0.79 and offers good calibration and discrimination across stratified risk groups in its validation cohort. DISCUSSION: The NIVO score outperformed pre-specified comparator scores. It is validated in a generalisable cohort and works despite the heterogeneity inherent to both this patient group and this intervention. Potential applications include informing discussions with patients and their families, aiding treatment escalation decisions, challenging pessimism and comparing risk-adjusted outcomes across centres.

Weekend admissions and mortality for major acute disorders across England and Wales: record linkage cohort studies.

BACKGROUND: To establish which major disorders are susceptible to increased mortality following acute admissions on weekends, compared with week days, and how this may be explained. METHODS: Cohorts based on national administrative inpatient and mortality data for 14,168,443 hospitalised patients in England and 913,068 in Wales who were admitted for 66 disorders that were associated with at least 200 deaths within 30 days of acute admission. The main outcome measure was the weekend mortality effect (defined as the conventional mortality odds ratio for admissions on weekends compared with week days). RESULTS: There were large, statistically significant weekend mortality effects (> 20%) in England for 22 of the 66 conditions and in both countries for 14. These 14 were 4 of 13 cancers (oesophageal, colorectal, lung and lymphomas); 4 of 13 circulatory disorders (angina, abdominal aortic aneurysm, peripheral vascular disease and arterial embolism & thrombosis); one of 8 respiratory disorders (pleural effusion); 2 of 12 gastrointestinal disorders (alcoholic and other liver disease); 2 of 3 ageing-related disorders (Alzheimer's disease and dementia); none of 7 trauma conditions; and one of 10 other disorders (acute renal failure). Across the disorders, 64% of the variation in weekend mortality effects in England and Wales was explained by reductions in admission rates at weekends and the medical disease category. CONCLUSIONS: The effect of weekend admission on 30 day mortality is seen mainly for cancers, some circulatory disorders, liver disease and a few other conditions which are mainly ageing- or cancer-related. Most of the increased mortality is associated with reduced admission rates at weekends and the medical disease category.

Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages.

OBJECTIVE: Vaping may increase the cytotoxic effects of e-cigarette liquid (ECL). We compared the effect of unvaped ECL to e-cigarette vapour condensate (ECVC) on alveolar macrophage (AM) function. METHODS: AMs were treated with ECVC and nicotine-free ECVC (nfECVC). AM viability, apoptosis, necrosis, cytokine, chemokine and protease release, reactive oxygen species (ROS) release and bacterial phagocytosis were assessed. RESULTS: Macrophage culture with ECL or ECVC resulted in a dose-dependent reduction in cell viability. ECVC was cytotoxic at lower concentrations than ECL and resulted in increased apoptosis and necrosis. nfECVC resulted in less cytotoxicity and apoptosis. Exposure of AMs to a sub-lethal 0.5% ECVC/nfECVC increased ROS production approximately 50-fold and significantly inhibited phagocytosis. Pan and class one isoform phosphoinositide 3 kinase inhibitors partially inhibited the effects of ECVC/nfECVC on macrophage viability and apoptosis. Secretion of interleukin 6, tumour necrosis factor α, CXCL-8, monocyte chemoattractant protein 1 and matrix metalloproteinase 9 was significantly increased following ECVC challenge. Treatment with the anti-oxidant N-acetyl-cysteine (NAC) ameliorated the cytotoxic effects of ECVC/nfECVC to levels not significantly different from baseline and restored phagocytic function. CONCLUSIONS: ECVC is significantly more toxic to AMs than non-vaped ECL. Excessive production of ROS, inflammatory cytokines and chemokines induced by e-cigarette vapour may induce an inflammatory state in AMs within the lung that is partly dependent on nicotine. Inhibition of phagocytosis also suggests users may suffer from impaired bacterial clearance. While further research is needed to fully understand the effects of e-cigarette exposure in humans in vivo, we caution against the widely held opinion that e-cigarettes are safe.

Metabolomic-based biomarker discovery for non-invasive lung cancer screening: A case study.

BACKGROUND: Lung cancer (LC) is one of the leading lethal cancers worldwide, with an estimated 18.4% of all cancer deaths being attributed to the disease. Despite developments in cancer diagnosis and treatment over the previous thirty years, LC has seen little to no improvement in the overall five year survival rate after initial diagnosis. METHODS: In this paper, we extended a recent study which profiled the metabolites in sputum from patients with lung cancer and age-matched volunteers smoking controls using flow infusion electrospray ion mass spectrometry. We selected key metabolites for distinguishing between different classes of lung cancer, and employed artificial neural networks and leave-one-out cross-validation to evaluate the predictive power of the identified biomarkers. RESULTS: The neural network model showed excellent performance in classification between lung cancer and control groups with the area under the receiver operating characteristic curve of 0.99. The sensitivity and specificity of for detecting cancer from controls were 96% and 94% respectively. Furthermore, we have identified six putative metabolites that were able to discriminate between sputum samples derived from patients suffering small cell lung cancer (SCLC) and non-small cell lung cancer. These metabolites achieved excellent cross validation performance with a sensitivity of 80% and specificity of 100% for predicting SCLC. CONCLUSIONS: These results indicate that sputum metabolic profiling may have potential for screening of lung cancer and lung cancer recurrence, and may greatly improve effectiveness of clinical intervention. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang.

Development of an algorithm for determining smoking status and behaviour over the life course from UK electronic primary care records.

BACKGROUND: Patients' smoking status is routinely collected by General Practitioners (GP) in UK primary health care. There is an abundance of Read codes pertaining to smoking, including those relating to smoking cessation therapy, prescription, and administration codes, in addition to the more regularly employed smoking status codes. Large databases of primary care data are increasingly used for epidemiological analysis; smoking status is an important covariate in many such analyses. However, the variable definition is rarely documented in the literature. METHODS: The Secure Anonymised Information Linkage (SAIL) databank is a repository for a national collection of person-based anonymised health and socio-economic administrative data in Wales, UK. An exploration of GP smoking status data from the SAIL databank was carried out to explore the range of codes available and how they could be used in the identification of different categories of smokers, ex-smokers and never smokers. An algorithm was developed which addresses inconsistencies and changes in smoking status recording across the life course and compared with recorded smoking status as recorded in the Welsh Health Survey (WHS), 2013 and 2014 at individual level. However, the WHS could not be regarded as a "gold standard" for validation. RESULTS: There were 6836 individuals in the linked dataset. Missing data were more common in GP records (6%) than in WHS (1.1%). Our algorithm assigns ex-smoker status to 34% of never-smokers, and detects 30% more smokers than are declared in the WHS data. When distinguishing between current smokers and non-smokers, the similarity between the WHS and GP data using the nearest date of comparison was κ = 0.78. When temporal conflicts had been accounted for, the similarity was κ = 0.64, showing the importance of addressing conflicts. CONCLUSIONS: We present an algorithm for the identification of a patient's smoking status using GP self-reported data. We have included sufficient details to allow others to replicate this work, thus increasing the standards of documentation within this research area and assessment of smoking status in routine data.

Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A Randomized Clinical Trial.

Importance: Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death. Objective: To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation. Design, Setting, and Participants: A randomized clinical trial of patients with persistent hypercapnia (Paco2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index [BMI] >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible. Interventions: There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min [interquartile range {IQR}, 0.5-2.0 L/min]) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min [IQR, 0.5-1.5 L/min]). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H2O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H2O, and a backup rate of 14 (IQR, 14-16) breaths/minute. Main Outcomes and Measures: Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI. Results: A total of 116 patients (mean [SD] age of 67 [10] years, 53% female, mean BMI of 21.6 [IQR, 18.2-26.1], mean [SD] forced expiratory volume in the first second of expiration of 0.6 L [0.2 L], and mean [SD] Paco2 while breathing room air of 59 [7] mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR, 0.5-3.9 months) in the home oxygen alone group, adjusted hazard ratio of 0.49 (95% CI, 0.31-0.77; P = .002). The 12-month risk of readmission or death was 63.4% in the home oxygen plus home NIV group vs 80.4% in the home oxygen alone group, absolute risk reduction of 17.0% (95% CI, 0.1%-34.0%). At 12 months, 16 patients had died in the home oxygen plus home NIV group vs 19 in the home oxygen alone group. Conclusions and Relevance: Among patients with persistent hypercapnia following an acute exacerbation of COPD, adding home noninvasive ventilation to home oxygen therapy prolonged the time to readmission or death within 12 months. Trial Registration: clinicaltrials.gov Identifier: NCT00990132.

Statement on smoking cessation in COPD and other pulmonary diseases and in smokers with comorbidities who find it difficult to quit.

Chronic obstructive pulmonary disease (COPD), lung cancer, asthma and pulmonary tuberculosis are common pulmonary diseases that are caused or worsened by tobacco smoking. Growing observational evidence suggests that symptoms and prognosis of these conditions improve upon smoking cessation. Despite increasing numbers of (small) randomised controlled trials suggesting intensive smoking cessation treatments work in people with pulmonary diseases many patients are not given specific advice on the benefits or referred for intensive cessation treatments and, therefore, continue smoking.This is a qualitative review regarding smoking cessation in patients with COPD and other pulmonary disorders, written by a group of European Respiratory Society experts. We describe the epidemiological links between smoking and pulmonary disorders, the evidence for benefits of stopping smoking, how best to assess tobacco dependence and what interventions currently work best to help pulmonary patients quit. Finally, we describe characteristics and management of any "hardcore" smoker who finds it difficult to quit with standard approaches.

Endothelial injury markers before and after nasal continuous positive airway pressure treatment for obstructive sleep apnoea hypopnoea syndrome.

PURPOSE: The purpose of this study was to evaluate whether serum amyloid A (SAA), C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) levels are elevated in obstructive sleep apnoea hypopnoea syndrome (OSAHS), and whether they change following acute- and medium-term CPAP treatment. METHODS: Consecutive subjects (n = 40) referred to the Sleep Disordered Breathing Unit were included in the research. Sera were sampled in the afternoon prior to an in-hospital limited-channel sleep study and on the next morning. Those diagnosed with OSAHS were commenced on CPAP and had further blood samples collected in the morning after the first night and then after a month of treatment. RESULTS: We had 20 subjects with moderate/severe OSAHS (mean ± SD), 4% desaturation rate (4% DR) 44.3 ± 31.4 events/h, and 20 comparator subjects with symptoms but negative sleep studies, 4% DR 5.6 ± 2.9 events/h. There was no difference in the morning and afternoon vascular injury marker levels between the OSAHS and comparator groups. However, CRP (6.52 ± 9.53 vs. 5.58 ± 8.47, p = 0.04) and VCAM-1 (366.30 ± 90.11 vs. 339.60 ± 95.87, p = 0.02) levels showed significant diurnal variation within the OSAHS group with higher afternoon levels compared to morning measurements. There were no changes in any of the vascular injury marker levels following CPAP. CONCLUSIONS: This study demonstrates that OSAHS leads to endothelial dysfunction as reflected by higher afternoon than morning CRP and VCAM-1 levels. However, despite a good CPAP compliance, a month of treatment does not decrease vascular injury marker levels.

COVID-19 managed on respiratory wards and intensive care units: Results from the national COVID-19 outcome report in Wales from March 2020 to December 2021.

BACKGROUND: A COVID-19 hospital guideline was implemented across all 18 acute hospitals in Wales in March 2020, promoting ward management of COVID pneumonitis and data collected across the first 3 Waves of the pandemic (Wave 1 March 1st 2020 to November 1st 2020, Wave 2 November 2st 2020 to February 21st 2021 and Wave 3 June 1st 2021 to December 14th 2021). The aim of this paper is to compare outcomes for patients by admission setting and type of ventilatory support given, with a particular focus on CPAP therapy. METHODS: This is a retrospective observational study of those aged over 18 admitted to hospital with community acquired COVID-19 between March 2020 and December 2021. The outcome of interest was in-hospital mortality. Univariate logistic regression models were used to compare crude outcomes across the waves. Multivariable logistic regression models were used to assess outcomes by different settings and treatments after adjusting for Wave, age, sex, co-morbidity and deprivation. RESULTS: Of the 7,803 records collected, 5,887 (75.4%) met the inclusion criteria. Analysis of those cases identified statistically significant outcome improvements across the waves for all patients combined (Waves 1 to 3: 31.5% to 18.8%, p<0.01), all ward patients (28.9% to 17.7%, p<0.01), and all ICU patients (44.3% to 32.2%, p = 0.03). Sub group analyses identified outcome improvements in ward patients without any oxygen therapy (Waves 1 to 3: 22.2% to 12.7%, p<0.01), with oxygen therapy only (34.0% to 12.9%, p<0.01) and with CPAP only (63.5% to 39.2%, p<0.01). The outcome improvements for ICU patients receiving CPAP only (35.7% to 24.6%, p = 0.31) or invasive ventilation (61.6% to 54.6%, p = 0.43) were not statistically significant though the numbers being admitted to ICU were small. The logistic regression models identified important age and comorbidity effects on outcomes. The multivariable model that took these into account suggested no statistically significantly greater risk of death for those receiving CPAP on the ward compared to those receiving CPAP in ICU (OR 0.89, 95% CI: 0.49 to 1.60). CONCLUSIONS: There were successive reductions in mortality in inpatients over the three Waves reflecting new treatments and better management of complications. Mortality for those requiring CPAP was similar in respiratory wards and ICUs after adjusting for differences in their respective patient populations.

Genomic attributes of airway commensal bacteria and mucosa.

Microbial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals. Clinically relevant genes encode antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. Using whole-genome content we identify dysbiotic features that may influence asthma and chronic obstructive pulmonary disease. We match isolate gene content to transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways to sustain host interactions with microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosa in lung diseases of global significance.

Quitting smoking improves two-year survival after a diagnosis of non-small cell lung cancer.

BACKGROUND: Smoking at diagnosis is associated with worse survival in lung cancer but the effects of quitting smoking on survival remain unclear. METHODS: In a UK multi-centre study (NCT01192256) we followed all 2751 patients with newly diagnosed non-small cell lung cancer (NSCLC) for up to 2 years or until death as part of the observational trial. Patients were offered smoking cessation advice and treatments according to national guidelines and local services. Smoking status was verified by exhaled carbon monoxide levels. Kaplan-Meier survival analysis and Cox Proportional Hazards Modelling examined the effects of quitting smoking on survival at 2 years. FINDINGS: 646 were current smokers at the time of diagnosis. The unadjusted two-year Kaplan-Meier survivor functions for quitters (0.45, 95 %CI 0.37 to 0.53) and continuers (0.32, 0.28 to 0.36) were significantly different (log-rank test p < 0.01). Median survival times were 659 days for quitters and 348 days for continuers. After adjusting for age, sex, stage, performance status, curative intent surgery, radical radiotherapy and comorbidity, the hazard ratio for quitting at diagnosis (0.75, 95 % CI 0.58 to 0.98) indicated a statistically significant reduction in the risk of death across the two-year study period. INTERPRETATION: Quitting smoking is independently and significantly associated with improved survival regardless of stage in NSCLC. We recommend that smoking cessation advice and treatments should be offered to smokers with lung cancer. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01192256. FUNDING: This work was supported by a 2010 Global Research Award for Nicotine Dependence (GRAND), Pfizer.

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study.

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect. INTERPRETATION: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. FUNDING: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.

Can telehealth help patients with COPD?

Chronic obstructive pulmonary disease (COPD) is a growing challenge for the NHS. New technologies, such as telehealth, offer opportunities for health and social care providers to look at innovative ways to manage the condition. Studies show telehealth services can reduce admissions and bed days, and boost patient satisfaction, but more research is needed to establish whether these technologies are safe, efficient and economical.

'I Live a Kind of Shadow Life': Individual Experiences of COVID-19 Recovery and the Impact on Physical Activity Levels.

Understanding of strategies to support individuals recovering from coronavirus disease 2019 (COVID-19) is limited. 'Long COVID' is a multisystem disease characterised by a range of respiratory, gastrointestinal, cardiovascular, neurological, and musculoskeletal symptoms extending beyond 12 weeks. The aim of this study was to explore individuals' experiences of recovering from COVID-19 to provide a better understanding of the acute and long-term impact of the disease on physical activity (PA). Individualised semi-structured interviews were conducted with 48 adults recovering from COVID-19 at 6-11 months post-infection. An inductive thematic analysis approach was used, reaching saturation at 14 interviews (10 female; 47 ± 7 years). Four overarching themes were identified: (i) Living with COVID-19, including managing activities of daily living; (ii) Dealing with the Unknown and self-management strategies; (iii) Re-introducing physical activity; and (iv) Challenges of returning to work. The return to PA, whether through activities of daily living, work or exercise, is often associated with the exacerbation of symptoms, presenting a range of challenges for individuals recovering from COVID-19. Individually tailored support is therefore required to address the unique challenges posed by COVID-19.

Evaluation of FTIR spectroscopy as a diagnostic tool for lung cancer using sputum.

BACKGROUND: Survival time for lung cancer is poor with over 90% of patients dying within five years of diagnosis primarily due to detection at late stage. The main objective of this study was to evaluate Fourier transform infrared spectroscopy (FTIR) as a high throughput and cost effective method for identifying biochemical changes in sputum as biomarkers for detection of lung cancer. METHODS: Sputum was collected from 25 lung cancer patients in the Medlung observational study and 25 healthy controls. FTIR spectra were generated from sputum cell pellets using infrared wavenumbers within the 1800 to 950 cm-1 "fingerprint" region. RESULTS: A panel of 92 infrared wavenumbers had absorbances significantly different between cancer and normal sputum spectra and were associated with putative changes in protein, nucleic acid and glycogen levels in tumours. Five prominent significant wavenumbers at 964 cm-1, 1024 cm-1, 1411 cm-1, 1577 cm-1 and 1656 cm-1 separated cancer spectra from normal spectra into two distinct groups using multivariate analysis (group 1: 100% cancer cases; group 2: 92% normal cases). Principal components analysis revealed that these wavenumbers were also able to distinguish lung cancer patients who had previously been diagnosed with breast cancer. No patterns of spectra groupings were associated with inflammation or other diseases of the airways. CONCLUSIONS: Our results suggest that FTIR applied to sputum might have high sensitivity and specificity in diagnosing lung cancer with potential as a non-invasive, cost-effective and high-throughput method for screening. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00899262.

Does home telemonitoring after pulmonary rehabilitation reduce healthcare use in optimized COPD? A pilot randomized trial.

AIM: To see if home telemonitors reduce healthcare use in those with optimized chronic obstructive pulmonary disease (COPD). METHODS: We randomized 40 stable patients with moderate to severe COPD, who had completed at least 12 sessions of outpatient pulmonary rehabilitation (PR), to receive standard care (Controls) for 52 weeks or standard care plus Docobo HealthHUB monitors at home for 26 weeks followed by 26 weeks standard care (Tm Group). During the monitoring period, the Tm Group completed symptoms and physical observations twice daily which were stored and then uploaded at 2 am through a freephone landline. Nurses could access the data through a secure web site and received alerting e-mails if certain combinations of data occurred. RESULTS: There were fewer primary care contacts for chest problems (p < 0.03) in the Tm group, but no differences between the groups in emergency room visits, hospital admissions, days in hospital or contacts to the specialist COPD community nurse team, during the monitoring period. After the monitors were removed, there were no differences between the groups for any of the health care contacts (p > 0.20 throughout). CONCLUSION: In stable, optimized COPD patients who have already completed PR, telemonitoring in addition to best care, reduces primary care chest contacts but not hospital or specialist team utilization.

ACCORD: A Multicentre, Seamless, Phase 2 Adaptive Randomisation Platform Study to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalised Patients: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Stage 1: To evaluate the safety and efficacy of candidate agents as add-on therapies to standard of care (SoC) in patients hospitalised with COVID-19 in a screening stage. Stage 2: To confirm the efficacy of candidate agents selected on the basis of evidence from Stage 1 in patients hospitalised with COVID-19 in an expansion stage. TRIAL DESIGN: ACCORD is a seamless, Phase 2, adaptive, randomised controlled platform study, designed to rapidly test candidate agents in the treatment of COVID-19. Designed as a master protocol with each candidate agent being included via its own sub-protocol, initially randomising equally between each candidate and a single contemporaneous SoC arm (which can adapt into 2:1). Candidate agents currently include bemcentinib, MEDI3506, acalabrutinib, zilucoplan and nebulised heparin. For each candidate a total of 60 patients will be recruited in Stage 1. If Stage 1 provides evidence of efficacy and acceptable safety the candidate will enter Stage 2 where a total of approximately 126 patients will be recruited into each study arm sub-protocol. Enrollees and outcomes will not be shared across the Stages; the endpoint, analysis and sample size for Stage 2 may be adjusted based on evidence from Stage 1. Additional arms may be added as new potential candidate agents are identified via candidate agent specific sub-protocols. PARTICIPANTS: The study will include hospitalised adult patients (≥18 years) with confirmed SARS-CoV-2 infection, the virus that causes COVID-19, that clinically meet Grades 3 (hospitalised - mild disease, no oxygen therapy), Grades 4 (hospitalised, oxygen by mask or nasal prongs) and 5 (hospitalised, non-invasive ventilation or high flow oxygen) of the WHO Working Group on the Clinical Characteristics of COVID-19 9-point category ordinal scale. Participants will be recruited from England, Northern Ireland, Wales and Scotland. INTERVENTION AND COMPARATOR: Comparator is current standard of care (SoC) for the treatment of COVID-19. Current candidate experimental arms include bemcentinib, MEDI3506, acalabrutinib, zilucoplan and nebulised heparin with others to be added over time. Bemcentinib could potentially reduce viral infection and blocks SARS-CoV-2 spike protein; MEDI3506 is a clinic-ready anti-IL-33 monoclonal antibody with the potential to treat respiratory failure caused by COVID; acalabrutinib is a BTK inhibitor which is anti-viral and anti-inflammatory; zilucoplan is a complement C5 inhibitor which may block the severe inflammatory response in COVID-19 and; nebulised heparin has been shown to bind with the spike protein. ACCORD is linked with the UK national COVID therapeutics task force to help prioritise candidate agents. MAIN OUTCOMES: Time to sustained clinical improvement of at least 2 points (from randomisation) on the WHO 9-point category ordinal scale, live discharge from the hospital, or considered fit for discharge (a score of 0, 1, or 2 on the ordinal scale), whichever comes first, by Day 29 (this will also define the "responder" for the response rate analyses). RANDOMISATION: An electronic randomization will be performed by Cenduit using Interactive Response Technology (IRT). Randomisation will be stratified by baseline severity grade. Randomisation will proceed with an equal allocation to each arm and a contemporaneous SoC arm (e.g. 1:1 if control and 1 experimental arm; 1:1:1 if two experimental candidate arms etc) but will be reviewed as the trial progresses and may be changed to 2:1 in favour of the candidate agents. BLINDING (MASKING): The trial is open label and no blinding is currently planned in the study. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This will be in the order of 60 patients per candidate agent for Stage 1, and 126 patients for Stage 2. However, sample size re-estimation may be considered after Stage 1. It is estimated that up to 1800 patients will participate in the overall study. TRIAL STATUS: Master protocol version ACCORD-2-001 - Master Protocol (Amendment 1) 22nd April 2020, the trial has full regulatory approval and recruitment is ongoing in the bemcentinib (first patient recruited 6/5/2020), MEDI3506 (first patient recruited 19/5/2020), acalabrutinib (first patient recruited 20/5/2020) and zilucoplan (first patient recruited 19/5/2020) candidates (and SoC). The recruitment dates of each arm will vary between candidate agents as they are added or dropped from the trial, but will have recruited and reported within a year. TRIAL REGISTRATION: EudraCT 2020-001736-95 , registered 28th April 2020. FULL PROTOCOL: The full protocol (Master Protocol with each of the candidate sub-protocols) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.