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Lung cancer (LC) is the most prevalent cancer worldwide, and responsible for over 1.3 million deaths each year. Currently, LC has a low five year survival rates relative to other cancers, and thus, novel methods to screen for and diagnose malignancies are necessary to improve patient outcomes. Here, we report on a pilot-sized study to evaluate the potential of the sputum microbiome as a source of non-invasive bacterial biomarkers for lung cancer status and stage. Spontaneous sputum samples were collected from ten patients referred with possible LC, of which four were eventually diagnosed with LC (LC+), and six had no LC after one year (LC-). Of the seven bacterial species found in all samples, Streptococcus viridans was significantly higher in LC+ samples. Seven further bacterial species were found only in LC-, and 16 were found only in samples from LC+. Additional taxonomic differences were identified in regards to significant fold changes between LC+ and LC-cases, with five species having significantly higher abundances in LC+, with Granulicatella adiacens showing the highest level of abundance change. Functional differences, evident through significant fold changes, included polyamine metabolism and iron siderophore receptors. G. adiacens abundance was correlated with six other bacterial species, namely Enterococcus sp. 130, Streptococcus intermedius, Escherichia coli, S. viridans, Acinetobacter junii, and Streptococcus sp. 6, in LC+ samples only, which could also be related to LC stage. Spontaneous sputum appears to be a viable source of bacterial biomarkers which may have utility as biomarkers for LC status and stage. [ABSTRACT FROM AUTHOR]

Objectives Developing screening and diagnosis methodologies based on novel biomarkers should allow for the detection of the lung cancer (LC) and possibly at an earlier stage and thereby increase the effectiveness of clinical interventions. Here, our primary objective was to evaluate the potential of spontaneous sputum as a source of non-invasive metabolomic biomarkers for LC status. Materials and methods Spontaneous sputum was collected and processed from 34 patients with suspected LC, alongside 33 healthy controls. Of the 34 patients, 23 were subsequently diagnosed with LC (LC + , 16 NSCLC, six SCLC, and one radiological diagnosis), at various stages of disease progression. The 67 samples were analysed using flow infusion electrospray ion mass spectrometry (FIE-MS) and gas-chromatography mass spectrometry (GC–MS). Results Principal component analysis identified negative mode FIE-MS as having the main separating power between samples from healthy and LC. Discriminatory metabolites were identified using ANOVA and Random Forest. Indications of potential diagnostic accuracy involved the use of receiver operating characteristic/area under the curve (ROC/AUC) analyses. This approach identified metabolites changes that were only observed with LC. Metabolites with AUC values of greater than 0.8 which distinguished between LC + /LC − binary classifications where identified and included Ganglioside GM1 which has previously been linked to LC. Conclusion This study indicates that metabolomics based on sputum can yield metabolites that can be used as a diagnostic and/or discriminator tool. These could aid clinical intervention and targeted diagnosis of LC within an ‘at risk’ LC − population group. The use of sputum as a non-invasive source of metabolite biomarkers may aid in the development of an at-risk population screening programme for lung cancer or enhanced clinical diagnostic pathways. [ABSTRACT FROM AUTHOR]

Chronic Obstructive Pulmonary Disease (COPD) is a major source of mortality and morbidity worldwide. The microbiome associated with this disease may be an important component of the disease, though studies to date have been based on sequencing of the 16S rRNA gene, and have revealed unequivocal results. Here, we employed metagenomic sequencing of the upper bronchial tract (UBT) microbiome to allow for greater elucidation of its taxonomic composition, and revealing functional changes associated with the disease. The bacterial metagenomes within sputum samples from eight COPD patients and ten ‘healthy’ smokers (Controls) were sequenced, and suggested significant changes in the abundance of bacterial species, particularly within the Streptococcus genus. The functional capacity of the COPD UBT microbiome indicated an increased capacity for bacterial growth, which could be an important feature in bacterial-associated acute exacerbations. Regression analyses correlated COPD severity (FEV1% of predicted) with differences in the abundance of Streptococcus pneumoniae and functional classifications related to a reduced capacity for bacterial sialic acid metabolism. This study suggests that the COPD UBT microbiome could be used in patient risk stratification and in identifying novel monitoring and treatment methods, but study of a longitudinal cohort will be required to unequivocally relate these features of the microbiome with COPD severity. [ABSTRACT FROM AUTHOR]

We conducted a six-month randomised controlled trial of home telemonitoring for patients with chronic obstructive pulmonary disease (COPD). A total of 40 stable patients with moderate to severe COPD who had completed pulmonary rehabilitation took part. They were randomised to receive standard care (controls) or standard care plus home telemonitoring (intervention). During the monitoring period, patients in the telemonitoring group recorded their symptoms and physical observations twice daily. The data were transmitted automatically at night via the home telephone line. Nurses could access the data through a website and receive alerting email messages if certain conditions were detected. The patients completed the St George's Respiratory Questionnaire, Hospital Anxiety and Depression and the EuroQoL EQ-5D quality of life scores before and after pulmonary rehabilitation, and then periodically during the trial. There were significant and clinically important improvements in the scores immediately following pulmonary rehabilitation, but thereafter there were no differences in quality of life scores between the groups at any time, or consistently within either group over time. The study showed that telemonitoring was safe but, despite being well used, it was not associated with changes in quality of life in patients who had stable COPD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Introduction: Many hospitals advise their smoking patients to contact a community-based stop smoking service. We investigated how well smokers attend a community-based service after receiving help from a hospital smoking cessation specialist (HSCS). [ABSTRACT FROM PUBLISHER]

The benefits of long-term oxygen therapy (LTOT) on mood in Chronic Obstructive Pulmonary Disease (COPD) are unproven. Longitudinal studies are affected by disease progression, the increased package of care (with LTOT) and may not control for known confounders on mood. We compared the point prevalence and severity of mood disturbance in patients with severe COPD, not on LTOT (the -LTOT group) to those with COPD on LTOT (the +LTOT group). We mailed the Hospital Anxiety and Depression (HAD) Score to 182 consecutive patients with severe COPD, identified from respiratory case notes in three UK Hospitals. We compared 57 patients not prescribed LTOT to 57 patients on LTOT, and used stratified sampling to match the groups as far as possible for age, gender, lung function and other possible confounders on mood. Or these, 25% of patients in both groups scored in the 'definite' case range for anxiety (HAD score ≥ 11). 37% of the -LTOT group and 33% of the +LTOT group scored in the 'definite' range for depression (HAD score ≥ 11) (p = N.S). In both groups, only 11% of responders were prescribed anxiolytics and/or antidepressants. Further multiregression analysis confirmed that socio-demographic variables (e.g., lives alone, feels isolated or recent life events) were stronger predictors of mood than the prescription of LTOT or other traditionally accepted factors such as co-morbidity or the use of antidepressants or anxiolytics. High levels of anxiety and depression are present in severe COPD and appear under-treated. The +LTOT and -LTOT patients had a similar high prevalence of anxiety and depression. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Interventions to improve treatment outcomes in sleep apnoea–hypopnoea syndrome (SAHS) have had mixed success. Most have concentrated on following the use of a continuous positive airway pressure (CPAP) machines; poorer users may not return for machine readings, so any compliance study must take into account rates of attendance rates. We hypothesised that a series of additional, early support measures would improve re-attendance over a sustained period. Patients and methods: Prospective, single-blinded interventional study. Seventy-two consecutive patients starting CPAP for SAHS were randomised to receive standard follow-up or extra early support. Attendance rates, CPAP use, Epworth scores, side-effects scores and number of changes to equipment were compared, by intent to treat, in both groups at 1 and 12 months. Results: Re-attendance rates were higher in the intervention group at 1month (P=0.04), 6 months (P=0.07) and 12 months (P=0.12). Those who defaulted tended previously to be poor users of the CPAP machine. For those who re-attended there was no difference in machine use or other outcomes. Conclusions: Simple interventions while commencing CPAP improve re-attendance with maximal benefit early on. This could provide more opportunities for solving problems early or considering alternative treatments. By confirming that poorer CPAP users eventually have higher default rates we recommend that future studies on CPAP compliance should first account for re-attendance rates. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • This study is the first to explore the potential cost-effectiveness of targeted SC intervention in currently smoking patients with newly diagnosed non–small cell lung cancer (a high-risk population proven to benefit from quitting smoking). • The LungCast trial (Clinical Trials Identifier NCT01192256) is a real-world data set exploring the prevalence and survival impact of smoking in a cohort of patients with newly diagnosed lung cancer with > 2400 patients tracked for up to 2 years (or until death). • This exploratory analysis can support commissioners in assessing the potential value of investing in dedicated SC services at the point of diagnosis of non–small cell lung cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: There is increasing interest in the cardiovascular pathology independently associated with chronic obstructive pulmonary disease (COPD). We examined the influence of long-term oxygen therapy (LTOT) on heart rate (RR) and QT time-series in COPD. Methods: Ten hypoxic stable COPD patients underwent Holter ECG monitoring for 24 h and physical activity/energy expenditure monitoring for 5 days before and after LTOT. Variability of RR and QT time-series was quantified using standard statistics and their structural (correlation/scaling) properties were assessed using multifractal analysis. Pre- and post-LTOT cardiac/activity parameters were compared to examine the influence of oxygen therapy and circadian variation. Results: PaO2 increased ( P = 0·0004) whilst PaCO2 was unchanged ( P = 0·56) following LTOT. Activity/energy expenditure estimates were also unchanged following LTOT ( P = 0·64–0·99), but RR variability was increased during the morning ( P < 0·05) and night ( P < 0·1, trend only). Multifractality of RR and QT time-series was not significantly changed following LTOT, although QT multifractality showed some time-dependent fluctuations. Trends in RR and QT time-series over 24-h were similar pre- and post-LTOT, indicating a generally normal circadian response. Conclusions: An increase in HRV following LTOT (but notably in the absence of altered activity levels) provides tentative evidence that LTOT has a direct effect on heart rate control in COPD. This beneficial influence was expressed mainly during the morning, and the relevance of this diurnal variation in response requires further investigation. It was also confirmed that both RR and (to a lesser degree) QT time-series in COPD have a multifractal structure, and this is not affected appreciably by LTOT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Highlights • Stopping smoking after a diagnosis of lung cancer can improve survival in patients with lung cancer. • Smoking cessation support uptake and abstinence rates in patients with lung cancer remains low. • Cessation should be advised in all smokers diagnosed with lung cancer. Abstract Objectives To update the prevalence of smoking in people as they were diagnosed with non-small cell lung cancer (NSCLC) and to see whether smoking status at baseline and quitting are independently associated with 1-year survival. Design A real-world cohort study following patients from diagnosis for up to 1 year or until death. Setting UK multi-centre study (28 sites) based in secondary and primary care. Participants 1124 patients with newly diagnosed NSCLC between 2010-2016. Main outcome measures Smoking status was validated at diagnosis and at every routine and emergency hospital visit. Cancer treatments were offered according to local multi-disciplinary team decisions following UK guidelines and smoking cessation treatments offered according to local practice /availability. Survival analysis and Cox Proportional Hazards Modelling examined the associations of a) smoking at baseline and b) quitting smoking, on survival at 1 year. Results 77% of never smokers, 60% of ex-smokers and 57% of current smokers, were alive at 1 year (p = 0.01). After adjusting for age, stage, EGOG, surgery and gender, ex smokers (adjusted HR 1.96, 95% CI 1.16–2.31) and current smokers (aHR 2.04, 1.19–3.48) were both more likely to die within one year. 23% of smokers with NSCLC quit within 3 months of diagnosis. At 1 year, 69% of those who quit were alive versus 53% of those who continued to smoke (p < 0.01). After adjusting the risk of dying was lower (aHR 0.75), in those who quit smoking, although this was not statistically significant (p = 0.23). Conclusions This is the largest prospective study that validates smoking in NSCLC; it shows a third of people are smoking at the time of diagnosis. Smokers have lower 12-month survival than never and ex -smokers. Quitting smoking was associated with 25% reduction in mortality which may be clinically important although not statistically significant, after adjusting for other factors. [ABSTRACT FROM AUTHOR]

Smoking at diagnosis is associated with worse survival in lung cancer but the effects of quitting smoking on survival remain unclear. 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. 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. 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. ClinicalTrials.gov , identifier NCT01192256. This work was supported by a 2010 Global Research Award for Nicotine Dependence (GRAND), Pfizer. [ABSTRACT FROM AUTHOR]

The lung microbiome has been shown to reflect a range of pulmonary diseases--for example: asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. Studies have now begun to show microbiological changes in the lung that correlate with lung cancer (LC) which could provide new insights into lung carcinogenesis and new biomarkers for disease screening. Clinical studies have suggested that infections with tuberculosis or pneumonia increased the risk of LC possibly through inflammatory or immunological changes. These have now been superseded by genomic-based microbiome sequencing studies based on bronchoalveolar lavage, sputum or saliva samples. Although some discrepancies exist, many have suggested changes in particular bacterial genera in LC samples particularly, Granulicatella, Streptococcus and Veillonella. Granulicatella is of particular interest, as it appeared to show LC stage-specific increases in abundance. We propose that these microbial community changes are likely to reflect biochemical changes in the LC lung, linked to an increase in anaerobic environmental niches and altered pyridoxal/polyamine/nitrogenous metabolism to which Granulicatella could be particularly responsive. These are clearly preliminary observations and many more expansive studies are required to develop our understanding of the LC microbiome. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]