Two datasets used to build the DEcancer pipelines from open access data. The tables in the cancerseek folder are uploaded for convenience and can also be found from the supplementary data of Early Cancer Detection from Multianalyte Blood Test Results paper. The nanoparticles dataset is processed with the Perseus software on the original data from Blume et al's Rapid, deep and precise profiling of the plasma proteome with multi-nanoparticle protein corona. These are distinct datasets in that the nanoparticles is a cohort of patients from a high dimensional, low sample size proteomics dataset.
Two datasets used to build the DEcancer pipelines from open access data. The tables in the cancerseek folder are uploaded for convenience and can also be found from the supplementary data of Early Cancer Detection from Multianalyte Blood Test Results paper. The nanoparticles dataset is processed with the Perseus software on the original data from Blume et al's Rapid, deep and precise profiling of the plasma proteome with multi-nanoparticle protein corona. These are distinct datasets in that the nanoparticles is a cohort of patients from a high dimensional, low sample size proteomics dataset.
Background The lack of standardised outcome assessments during hospitalisation and follow-up for acute COPD exacerbations has hampered scientific progress and clinical proficiency. The objective of the present study was to evaluate patients’ acceptance of selected outcome and experience measurements during hospitalisations for COPD exacerbations and follow-up. Methods An online survey was held amongst COPD patients in France, Belgium, The Netherlands, Germany and the UK. The European Lung Foundation COPD Patient Advisory Group was involved in the conceptualisation, development and dissemination of the survey. The survey was complementary to a previously obtained expert consensus. We assessed patients’ views and acceptance of selected patient-reported outcomes or experiences and corresponding measurement instruments (for dyspnoea, frequent productive cough, health status and hospitalisation experience), and of selected clinical investigations (blood draw, pulmonary function test, 6-min walk test, chest computed tomography, echocardiography). Findings 200 patients completed the survey. All selected outcomes and experiences were deemed important, and acceptance of their methods of assessment was high. The modified Medical Research Council scale and a numerical rating scale to address dyspnoea, the COPD Assessment Test for quality of life and frequent productive cough, and the Hospital Consumer Assessment of Healthcare Providers and Systems for hospital experiences were the instruments preferred by patients. Consensus on importance of blood draw and spirometry was higher compared with the other investigations. Interpretation The survey results endorse the use of the selected outcome and experience measurements during hospitalisations for COPD exacerbations. They can be used to optimise standardised and patient-centred care and facilitate multicentric data collection.
Background
Multiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness.
Methods
We conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment.
Results
146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportions 0.131, 95% CI (0.043 to 0.218), p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever
and proportion of participants with at least 1 day of fever was significantly lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care. Budesonide was safe with only 5 (7%) of participants reporting self-limiting adverse events.
Conclusion
Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection.
(ClinicalTrials.gov number, NCT04416399)
(Funded by Oxford NIHR Biomedical Research Centre and AstraZeneca)
Background COPD and asthma exacerbations result in many emergency department admissions. Not all treatments are successful, often leading to hospital readmissions. Aims We sought to develop predictive models for exacerbation treatment outcome in a cohort of exacerbating asthma and COPD patients presenting to the emergency department. Methods Treatment failure was defined as the need for additional systemic corticosteroids (SCS) and/or antibiotics, hospital readmissison or death within 30 days of initial emergency department visit. We performed univariate analysis comparing characteristics of patients either given or not given SCS at exacerbation and of patients who succeeded versus failed treatment. Patient demographics, medications and exacerbation symptoms, physiology and biology were available. We developed multivariate random forest models to identify predictors of SCS prescription and for predicting treatment failure. Results Data were available for 81 patients, 43 (53%) of whom failed treatment. 64 (79%) of patients were given SCS. A random forest model using presence of wheeze at exacerbation and blood eosinophil percentage predicted SCS prescription with area under receiver operating characteristic curve (AUC) 0.69. An 11 variable random forest model (which included medication, previous exacerbations, symptoms and quality of life scores) could predict treatment failure with AUC 0.81. A random forest model using just the two best predictors of treatment failure, namely, visual analogue scale for breathlessness and sputum purulence, predicted treatment failure with AUC 0.68. Conclusion Prediction of exacerbation treatment outcome can be achieved via supervised machine learning combining different predictors at exacerbation. Validation of our predictive models in separate, larger patient cohorts is required.
Abstract Background Multiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness. Methods We conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. Results 146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care. Conclusion Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection. (Funded by Oxford NIHR Biomedical Research Centre and AstraZeneca; ClinicalTrials.gov number, NCT04416399 ) Research in context Evidence before this study The majority of interventions studied for the COVID-19 pandemic are focused on hospitalised patients. Widely available and broadly relevant interventions for mild COVID-19 are urgently needed. Added value of this study In this open label randomised controlled trial, inhaled budesonide, when given to adults with early COVID-19 illness, reduces the likelihood of requiring urgent care, emergency department consultation or hospitalisation. There was also a quicker resolution of fever, a known poor prognostic marker in COVID-19 and a faster self-reported and questionnaire reported symptom resolution. There were fewer participants with persistent COVID-19 symptoms at 14 and 28 days after budesonide therapy compared to usual care. Implications of all the available evidence The STOIC trial potentially provides the first easily accessible effective intervention in early COVID-19. By assessing health care resource utilisation, the study provides an exciting option to help with the worldwide pressure on health care systems due to the COVID-19 pandemic. Data from this study also suggests a potentially effective treatment to prevent the long term morbidity from persistent COVID-19 symptoms.
Chronic obstructive pulmonary disease (COPD) affects millions of people worldwide.It is now clear that COPD is heterogeneous, different components of the disease being present in different patients.Yet, the diversity of COPD pathophysiology, severity and how this relates to disease prognosis and treatment outcomes is far from understood.In order to address this, mathematical techniques such as cluster analysis have been employed to identify subgroups or clusters of COPD patients with differing disease attribute profiles.However, significant methodological shortcomings call into question the validity of the COPD clusters identified in such studies.Furthermore, few published studies relate COPD clusters to underlying disease mechanisms and treatment outcomes.Where this has been addressed, progress has particularly been made for patients with an eosinophilic-predominant profile.In order to maximise the usefulness of COPD cluster analysis studies, we propose that future studies must implement more stringent methodologies and focus on COPD inflammatory biology.
Cancer is a leading cause of mortality worldwide. Over 50% of cancers are diagnosed late, rendering many treatments ineffective. Existing liquid biopsy studies demonstrate a minimally invasive and inexpensive approach for disease detection but lack parsimonious biomarker selection, exhibit poor cancer detection performance and lack appropriate validation and testing. We established a tailored machine learning pipeline, DEcancer, for liquid biopsy analysis that addresses these limitations and improved performance. In a test set from a published cohort of 1,005 patients including 8 cancer types and 812 cancer-free individuals, DEcancer increased stage 1 cancer detection sensitivity across cancer types from 48 to 90%. In addition, with a test set cohort of patients from a high dimensional proteomics dataset of 61 lung cancer patients and 80 cancer-free individuals, DEcancer's performance using a 14-43 protein panel was comparable to 1,000 original proteins. DEcancer is a promising tool which may facilitate improved cancer detection and management.
Despite hospitalization for exacerbation being a high-risk event for morbidity and mortality, there is little consensus globally regarding the assessment and management of hospitalised exacerbations of COPD. We aimed to establish a consensus list of symptoms, physiological measures, clinical scores, patient questionnaires and investigations to be obtained at time of hospitalised COPD exacerbation and follow-up.A modified Delphi online survey with pre-defined consensus of importance, feasibility and frequency of measures at hospitalisation and follow-up of a COPD exacerbation was undertaken.A total of 25 COPD experts from 18 countries contributed to all 3 rounds of the survey. Experts agreed that a detailed history and examination were needed. Experts also agreed on which treatments are needed and how soon these should be delivered. Experts recommended that a full blood count, renal function, C-reactive protein and cardiac blood biomarkers (BNP and troponin) should be measured within 4 hours of admission and that the modified Medical Research Council dyspnoea scale (mMRC) and COPD assessment test (CAT) should be performed at time of exacerbation and follow-up. Experts encouraged COPD clinicians to strongly consider discussing palliative care, if indicated, at time of hospitalisation.This Europe-wide consensus document is the first attempt to standardise the assessment and care of patients hospitalised for COPD exacerbations. This should be regarded as the starting point to build knowledge and evidence on patients hospitalised for COPD exacerbations.
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