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Burns inhalation injury increases the attributable mortality of burns related trauma. However, diagnostic uncertainties around bronchoscopically graded severity, and its effect on outcomes, remain. This study evaluated the impact of different bronchoscopic burns inhalation injury grades on outcomes.A single-centre cohort study of all patients admitted to the London Burns centre intensive care unit (BICU) over 12 years. Demographic data, burn and burns inhalation injury characteristics, and ICU-related parameters were collected retrospectively. The primary outcome was mortality. Secondary outcomes were hospital and ICU lengths of stay. The impact of pneumonia was determined. Univariate and multivariable Cox's proportional hazards regression analyses informed factors predicting mortality.Burns inhalation injury was diagnosed in 84 of 231 (36%) critically ill burns patients; 20 mild (grade 1), 41 severe (grades 2/3) and 23 unclassified bronchoscopically. Median (IQR) total body surface area burned (TBSA) was 20% (10-40). Mortality was significantly higher in patients with burns inhalation injury vs those without burns inhalation injury (38/84 [45%] vs 35/147 [24%], p 0.001). Patients with pneumonia had a higher mortality than those without (34/125 [27%] vs 8/71 [11%], p = 0.009). In multivariable analysis, severe burns inhalation injury significantly increased mortality (adjusted HR=2.14, 95%CI: 1.12-4.09, p = 0.022), compared with mild injury (adjusted HR=0.58, 95% CI: 0.18-1.86, p = 0.363). Facial burns (adjusted HR=3.13, 95%CI: 1.69-5.79, p 0.001), higher TBSA (adjusted HR=1.05, 95%CI: 1.04-1.06, p 0.001) and older age (adjusted HR=1.04, 95%CI: 1.02-1.07, p 0.001) also independently predicted mortality, though pneumonia did not.Severe burns inhalation injury is a significant risk factor for mortality in critically ill burns patients. However, pneumonia did not increase mortality from burns inhalation injury. This work confirms prior implications of bronchoscopically graded burns inhalation injury. Further study is suggested, through registries, into the diagnostic accuracy and reliability of bronchoscopy in burns related lung injury.

Background The FilmArray Pneumonia Panel (bioMérieux) is a rapid multiplex PCR aiming to increase speed and sensitivity in the microbiological diagnosis of pneumonia. This offers potential for improved antimicrobial stewardship and evidence-based antibiotic prescribing. Whether such gains can be realised in practise is uncertain, thus, we conducted a randomized controlled trial to examine this. Methods Adults and children in ICU with suspected hospital-acquired or ventilator-associated pneumonia were randomized to standard care or a FilmArray Pneumonia Panel PCR test at the point of care supported by an optional prescribing algorithm. Participants were followed for 28 days. FilmArray tests were run retrospectively in the control-arm but results were not provided to treating clinicians. Antimicrobial therapy was adjudged by a committee of blinded, independent microbiologists for ‘activity’ and ‘proportionality’ vs. pathogens detected in each arm regardless of the time and method by which they were found. Clinical cure was not blinded and judged by site PI according to defined clinical parameters. Results Between July 2019 and August 2021, 556 participants were randomized at 13 hospitals; 545 met eligibility criteria; 92 were children and 183 had COVID-19 at enrolment. Baseline characteristics were well balanced between study arms. In the intervention arm 76.5% of participants were judged to have received active and proportionate antibiotics at 24h vs. 55.9% in the control arm (p< 0.001); proportions at 72h were 73.4% and 58.8%, respectively p< 0.001). Site-reported clinical cure of pneumonia at 14 days was 56.7% in the intervention arm and 64.7% in the control arm (95% CI -0.15 to 0.02), with exploratory analyses suggesting site heterogeneity. 28-day mortality was 31.3% in the intervention arm and 28.2% in the control arm (p = 0.098). Median ventilator-free days by Day 21 were 2 days in both study arms. Median ICU length of stay was 14 days in both arms. Conclusion Use of the FilmArray Pneumonia Panel PCR led to a significant increase in the proportion of patients receiving ‘active and proportionate’ antibiotic therapy at 24h. Reasons for lower reported clinical cure, despite better tailored antibiotic use, remain under active analysis. Disclosures Virve Enne, BSc PhD, Biomerieux: Advisor/Consultant|Biomerieux: Advisor/Consultant|Biomerieux: Grant/Research Support|Biomerieux: Grant/Research Support|Inflammatix: Grant/Research Support Juliet High, Masters in Chemistry, Biomerieux: Advisor/Consultant|Biomerieux: Grant/Research Support David Brealey, MBBSPhD, Biomerieux: Honoraria David Livermore, BSc PhD, bioMerieux: Honoraria|bioMerieux: Provision of machines/test kits for INHALE.

Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications.

BACKGROUND Panton-Valentine leukocidin (PVL) is an exotoxin secreted by Staphylococcus aureus (S. aureus), responsible for skin and soft tissue infections. As a cause of severe necrotising pneumonia, it is associated with a high mortality rate. A rare entity, the epidemiology of PVL S. aureus (PVL-SA) pneumonia as a complication of influenza coinfection, particularly in young adults, is incompletely understood. CASE SUMMARY An adolescent girl presented with haemoptysis and respiratory distress, deteriorated rapidly, with acute respiratory distress syndrome (ARDS) and profound shock requiring extensive, prolonged resuscitation, emergency critical care and venovenous extracorporeal membrane oxygenation (ECMO). Cardiac arrest and a rare complication of ECMO cannulation necessitated intra-procedure extracorporeal cardiopulmonary resuscitation, i.e., venoarterial ECMO. Coordinated infectious disease, microbiology and Public Health England engagement identified causative agents as PVL-SA and influenza A/H3N2 from bronchial aspirates within hours. Despite further complications of critical illness, the patient made an excellent recovery with normal cognitive function. The coordinated approach of numerous multidisciplinary specialists, nursing staff, infection control, specialist cardiorespiratory support, hospital services, both adult and paediatric and Public Health are testimony to what can be achieved to save life against expectation, against the odds. The case serves as a reminder of the deadly nature of PVL-SA when associated with influenza and describes a rare complication of ECMO cannulation. CONCLUSION PVL-SA can cause severe ARDS and profound shock, with influenza infection. A timely coordinated multispecialty approach can be lifesaving.

Background Antimicrobial overuse causes increased antimicrobial resistance in ICUs; antimicrobial stewardship programmes (ASPs) aim to optimize usage. Following an MDR Acinetobacter baumannii (MRAb) outbreak in 2008, an ASP was implemented at a London ICU, and then continued as a long-term programme. This study aimed to determine long-term changes in antimicrobial prescribing 9 years on. Methods Data were collected from ICU patients in 2008 immediately before ASP implementation, and thereafter for 6 month cohort periods in 2010–2011, 2012 and 2017. Antimicrobial usage in DDD per 1000 occupied bed days (OBD) were compared. Multivariate linear regression models for antimicrobial days were fitted, adjusting for APACHE II score and patient days. Antimicrobial resistance in Pseudomonas aeruginosa (as an indicator organism) was compared across cohort periods. Findings Across 400 patients over 9 years, antimicrobial use changed significantly (P Conclusions Following ASP implementation after an outbreak of MRAb, reduced antimicrobial prescribing was maintained 9 years on. We identify several factors influencing successful long-term maintenance of ASPs in ICUs.

INTRODUCTION: Rapid Point of Care Tests for infection (POCT) do not consistently improve antibiotic stewardship (ASP) of suspected ICU infection. We measured 1) the effect of a negative PCR-POCT on antibiotic stop decisions, and 2) clinico-behavioural factors that prevent stopping.METHODS: Vignettes of antibiotic treated respiratory infection, with 4 distinct trajectories were presented to ICU clinicians: overall improvement, clinical improvement/biological worsening, clinical worsening/biological improvement, overall worsening. Initial and post PCR-POCT antibiotic decisions (stop or continue) /confidence levels were recorded. The PCR-POCT offer was voluntary but always presented and negative. Linear regression determined association of their final decision with influencing factors.RESULTS: Seventy clinicians responded. A negative PCR-POCT increased stop decisions in all scenarios (pimprovement (already high); especially in discordant clin worse(49% pre-POCT vs 74% post-POCT). Inclination to stop was reduced by an ambiguous/worsening trajectory(p=0.015), initial confidence to continue(pp CONCLUSIONS: Negative PCR-POCT increases the inclination to stop antibiotics, particularly in ambiguous/worsening trajectories of ICU infection. Clinician intuition to continue and disinterest in POCT reduce its influence to stop. Highlighting and quantifying the predictive impact of behavioural-trajectorial factors can improve antibiotic stewardship and study design in ICU related infection.

AIMS: Comprehensive echocardiography assessment of right ventricular (RV) impairment has not been reported in critically ill patients with COVID-19. We detail the specific phenotype and clinical associations of RV impairment in COVID-19 acute respiratory distress syndrome (ARDS). METHODS: Transthoracic echocardiography (TTE) measures of RV function were collected in critically unwell patients for associations with clinical, ventilatory and laboratory data. RESULTS: Ninety patients (25.6% female), mean age 52.0 ± 10.8 years, veno-venous extracorporeal membrane oxygenation (VVECMO) (42.2%) were studied. A significantly higher proportion of patients were identified as having RV dysfunction by RV fractional area change (FAC) (72.0%,95% confidence interval (CI) 61.0-81.0) and RV velocity time integral (VTI) (86.4%, 95 CI 77.3-93.2) than by tricuspid annular plane systolic excursion (TAPSE) (23.8%, 95 CI 16.0-33.9), RVS' (11.9%, 95% CI 6.6-20.5) or RV free wall strain (FWS) (35.3%, 95% CI 23.6-49.0). RV VTI correlated strongly with RV FAC (p ≤ 0.01). Multivariate regression demonstrated independent associations of RV FAC with NTpro-BNP and PVR. RV-PA coupling correlated with PVR (univariate p

OBJECTIVES: Severe coronavirus disease 2019 is associated with an extensive pneumonitis and frequent coagulopathy. We sought the true prevalence of thrombotic complications in critically ill patients with severe coronavirus disease 2019 on the ICU, with or without extracorporeal membrane oxygenation. DESIGN: We undertook a single-center, retrospective analysis of 72 critically ill patients with coronavirus disease 2019-associated acute respiratory distress syndrome admitted to ICU. CT angiography of the thorax, abdomen, and pelvis were performed at admission as per routine institution protocols, with further imaging as clinically indicated. The prevalence of thrombotic complications and the relationship with coagulation parameters, other biomarkers, and survival were evaluated. SETTING: Coronavirus disease 2019 ICUs at a specialist cardiorespiratory center. PATIENTS: Seventy-two consecutive patients with coronavirus disease 2019 admitted to ICU during the study period (March 19, 2020, to June 23, 2020). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All but one patient received thromboprophylaxis or therapeutic anticoagulation. Among 72 patients (male:female = 74%; mean age: 52 ± 10; 35 on extracorporeal membrane oxygenation), there were 54 thrombotic complications in 42 patients (58%), comprising 34 pulmonary arterial (47%), 15 peripheral venous (21%), and five (7%) systemic arterial thromboses/end-organ embolic complications. In those with pulmonary arterial thromboses, 93% were identified incidentally on first screening CT with only 7% suspected clinically. Biomarkers of coagulation (e.g., D-dimer, fibrinogen level, and activated partial thromboplastin time) or inflammation (WBC count, C-reactive protein) did not discriminate between patients with or without thrombotic complications. Fifty-one patients (76%) survived to discharge; 17 (24%) patients died. Mortality was significantly greater in patients with detectable thrombus (33% vs 10%; p = 0.022). CONCLUSIONS: There is a high prevalence of thrombotic complications, mainly pulmonary, among coronavirus disease 2019 patients admitted to ICU, despite anticoagulation. Detection of thrombus was usually incidental, not predicted by coagulation or inflammatory biomarkers, and associated with increased risk of death. Systematic CT imaging at admission should be considered in all coronavirus disease 2019 patients requiring ICU.

Rationale: Clinical and epidemiologic data in coronavirus disease (COVID-19) have accrued rapidly since the outbreak, but few address the underlying pathophysiology. Objectives: To ascertain the physiologic, hematologic, and imaging basis of lung injury in severe COVID-19 pneumonia. Methods: Clinical, physiologic, and laboratory data were collated. Radiologic (computed tomography (CT) pulmonary angiography [n = 39] and dual-energy CT [DECT, n = 20]) studies were evaluated: observers quantified CT patterns (including the extent of abnormal lung and the presence and extent of dilated peripheral vessels) and perfusion defects on DECT. Coagulation status was assessed using thromboelastography. Measurements and Results: In 39 consecutive patients (male:female, 32:7; mean age, 53 ± 10 yr [range, 29–79 yr]; Black and minority ethnic, n = 25 [64%]), there was a significant vascular perfusion abnormality and increased physiologic dead space (dynamic compliance, 33.7 ± 14.7 ml/cm H2O; Murray lung injury score, 3.14 ± 0.53; mean ventilatory ratios, 2.6 ± 0.8) with evidence of hypercoagulability and fibrinolytic “shutdown”. The mean CT extent (±SD) of normally aerated lung, ground-glass opacification, and dense parenchymal opacification were 23.5 ± 16.7%, 36.3 ± 24.7%, and 42.7 ± 27.1%, respectively. Dilated peripheral vessels were present in 21/33 (63.6%) patients with at least two assessable lobes (including 10/21 [47.6%] with no evidence of acute pulmonary emboli). Perfusion defects on DECT (assessable in 18/20 [90%]) were present in all patients (wedge-shaped, n = 3; mottled, n = 9; mixed pattern, n = 6). Conclusions: Physiologic, hematologic, and imaging data show not only the presence of a hypercoagulable phenotype in severe COVID-19 pneumonia but also markedly impaired pulmonary perfusion likely caused by pulmonary angiopathy and thrombosis.

Background UK data suggest 6% of COVID-19 hospital admissions are either currently pregnant or immediately post-partum. However, the current literature suggests that if COVID-19 occurs in pregnancy, or post-partum, symptoms are mostly mild. Methods All COVID-19 admissions to one acute London National Health Service Foundation trust were reviewed since the beginning of the COVID-19 pandemic to 1 May 2020 to establish whether there were any pregnant or immediately post-partum admissions. Data were extracted from hospital electronic records and anonymised. Any patients admitted to adult intensive care unit had their case notes reviewed in detail and comparison made to a local risk-assessment guideline identifying patients at-risk of thromboembolic events or cytokine storms. Local hospital guidelines were followed. Patients admitted to adult intensive care unit gave written consent. Results A total of 24 pregnant or immediately post-partum patients with COVID-19 were admitted. Three patients required long adult intensive care unit admissions for severe single-organ respiratory failure after emergency C-sections. Two of these patients required proning (three times and eight times, respectively). All were considered medium risk for thromboembolic events but had rising D-dimers following adult intensive care unit admission, resulting in increased dosing of pharmacological thromboprophylaxis throughout their admission. All were considered low risk for a cytokine storm, and none had any significant cardiovascular or renal involvement. One patient developed a super-imposed fungal lung infection. All three patients developed delirium following cessation of sedation. Conclusion Pregnant or immediately post-partum women can develop severe COVID-19 symptoms requiring prolonged adult intensive care unit admission. It is likely to be single-organ failure, but patients are at a high risk of a thromboembolic event and delirium.

The year 2016 marks the 200th anniversary of Laennec's invention of the stethoscope, with the subsequent publication of auscultatory sounds for clinical diagnosis in 1819. Today, history and examination remain pivotal to accurate diagnosis. The hypotheticodeductive method of diagnosis based on Bayes' theorem requires a detailed history and examination skills to elicit symptoms and signs. The key symptoms of respiratory disease are breathlessness, chest pain, wheeze, cough and associated sputum production. Non-respiratory conditions may also produce such symptoms. A systematic approach to history-taking should include all primary symptoms, their time-course, characteristics, severity and trajectory. A review of non-respiratory associations, pharmaceutical and historical aspects of respiratory symptoms should precede a thorough review of clinical signs. Further questioning or examination will lead to assimilation of information, synthesis with clinicopathophysiological knowledge of respiratory diseases, and formulation of a differential diagnosis. On examination, based on the model of inspection, palpation, percussion and auscultation, there are a few classical patterns of the most important focal abnormalities, although there may be an absence of clinical signs. This article reviews the key features of respiratory symptoms and signs, outlines tips on how best to elicit these, and discusses patterns of clinical features suggesting certain diagnoses.

BackgroundEarly studies of veno-venous extracorporeal membrane oxygenation (VV-ECMO) in COVID-19 have revealed similar outcomes to historical cohorts. Changes in the disease and treatments has led to differences in the patients supported on VV-ECMO in the 1st and 2nd waves. We aimed to compare these two groups in both the acute and follow-up phase.MethodsIn this retrospective study, we identified the differences between patients supported on ECMO for COVID-19 between wave 1 (17/03/2020-31/08/2020) and wave 2 (01/09/2020-25/05/2021). We examined mortality at censoring date (30/11/2021) and decannulation, patient characteristics, complications and lung function and quality of life (QOL – by EQ5D3L) at first follow-up.FindingsOne-hundred and twenty-three patients were included in our analysis. Survival at censoring date [Chi-sqaured 6.35, p=0.012] and decannulation [90.4% vs 70.0%, pnd wave, whilst duration of ECMO run was longer [12.0(18.0-30.0) days vs. 29.5(15.5-58.3)] days (p=0.005)). Wave 2 patients had longer application of non-invasive ventilation (NIV) prior to ECMO and a higher incidence of barotrauma. Patient age and NIV use were independently associated with increased mortality [OR 1.07(1.01-1.14), p=0.025 and 3.37(1.12–12.60), p=0.043 respectively]. QOL and lung function, apart from KCOc was similar at follow up across the waves.ConclusionMost patients with COVID-19 supported on ECMO in both waves survived in the short and longer term. At follow-up patients had similar lung function and QOL across the 2 waves. This suggests that ECMO has an ongoing role in the management of a carefully selected group of patients with COVID-19.Trial RegistrationResearch Ethics Committee (20/EM/0204)

Persistent interstitial lung changes with associated symptoms occur in a proportion of individuals that have recovered from severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) infection through unknown mechanisms. We studied individuals with severe COVID-19 longitudinally following recovery from acute illness. Subjects with interstitial lung changes at 3-6 months post-recovery had an upregulated neutrophil-associated immune signature including increased chemokines, proteases and markers of neutrophil extracellular traps detectable systemically. Similar pathways were enriched in the upper airway with a concomitant augmentation of antiviral type-I interferon signalling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Repeat sampling indicated that full normalisation of radiological and functional changes has not yet been reached in many individuals by 12 months post-recovery. These data provide functional insight into mechanisms driving pulmonary sequelae of COVID-19 and provide a rational basis for development of future targeted approaches to prevent long-term complications.

PurposeTo describe the incidence of pulmonary artery thrombosis in COVID-19 versus influenza pneumonia using CT angiography and to assess whether it may increase the risk of pulmonary hypertension.Materials and MethodsSingle and dual energy CT pulmonary angiography of age- and gender-matched patients with influenza and COVID-19 pneumonia, referred for extra-corporeal membrane oxygenation (ECMO) and/or mechanical ventilation from January 2016 to January 2021, were retrospectively evaluated. Two independent observers qualitatively and quantitively assessed clot burden and Qanadli CT Obstruction Index. Two consensus observers calculated pulmonary artery volume and right to left ventricular diameter ratio (Terarecon, California, USA) to diagnose pulmonary hypertension. Pulmonary infarct volume and perfused blood volume relative enhancement were also calculated (Syngo via, Siemens Healthineers, Forchheim, Germany). All radiologic parameters were correlated with clinical data. To assess if in situ thrombosis could be visualised on CT, isolated segmental and subsegmental filling defects were used as an imaging surrogate. For statistical analyses, Graphpad Prism9 and IBM SPSS v27.0 software were used.ResultsThe incidence of either central PE or DVT was equal between patients with COVID-19 and influenza pneumonia (20%). The incidence of isolated segmental and subsegmental filling defects was higher in COVID-19 but without statistical significance (44% vs 32%;p=0.5607). Right to left ventricular diameter and pulmonary artery to aorta ratios were higher in COVID-19 compared to influenza (1.01 vs 0.866 and 1.04 vs 0.904;p=0.0071 and p=0.0023, respectively).ConclusionIn a comparable group of patients with severe COVID-19 and influenza pneumonia, CT features of pulmonary hypertension are more often present in patients with COVID-19 pneumonia despite an equal clot burden on CT. This is not attributable to pulmonary thrombosis visible on CT and supports the hypothesis that micro- rather than macrovascular obstruction is the cause of severe hypoxia in COVID-19 pneumonia.

A significant proportion of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) with high risk of death. The efficacy of veno-venous extracorporeal membrane oxygenation (VV-ECMO) for COVID-19 on longer-term outcomes, unlike in other viral pneumonias, is unknown. In this study, we aimed to compare the 6 month mortality of patients receiving VV-ECMO support for COVID-19 with a historical viral ARDS cohort. Fifty-three consecutive patients with COVID-19 ARDS admitted for VV-ECMO to the Royal Brompton Hospital between March 17, 2020 and May 30, 2020 were identified. Mortality, patient characteristics, complications, and ECMO parameters were then compared to a historical cohort of patients with non-COVID-19 viral pneumonia. At 6 months survival was significantly higher in the COVID-19 than in the non-COVID-19 viral pneumonia cohort (84.9% vs. 66.0%, p = 0.040). Patients with COVID-19 had an increased Murray score (3.50 vs. 3.25, p = 0.005), a decreased burden of organ dysfunction (sequential organ failure score score [8.76 vs. 10.42, p = 0.004]), an increased incidence of pulmonary embolism (69.8% vs. 24.5%, p < 0.001) and in those who survived to decannulation longer ECMO runs (19 vs. 11 days, p = 0.001). Our results suggest that survival in patients supported with EMCO for COVID-19 are at least as good as those treated for non-COVID-19 viral ARDS.

Background Rapid molecular diagnostic tests to investigate the microbial aetiology of pneumonias may improve treatment and antimicrobial stewardship in intensive care units (ICUs). Clinicians’ endorsement and uptake of these tests is crucial to maximise engagement; however, adoption may be impeded if users harbour unaddressed concerns or if device usage is incompatible with local practice. Accordingly, we strove to identify ICU clinicians’ beliefs about molecular diagnostic tests for pneumonias before implementation at the point-of-care. Methods We conducted semi-structured interviews with 35 critical care doctors working in four ICUs in the United Kingdom. A clinical vignette depicting a fictitious patient with signs of pneumonia was used to explore clinicians’ beliefs about the importance of molecular diagnostics and their concerns. Data were analysed thematically. Results Clinicians’ beliefs about molecular tests could be grouped into two categories: perceived potential of molecular diagnostics to improve antibiotic prescribing (Molecular Diagnostic Necessity) and concerns about how the test results could be implemented into practice (Molecular Diagnostic Concerns). Molecular Diagnostic Necessity stemmed from beliefs that positive results would facilitate targeted antimicrobial therapy; that negative results would signal the absence of a pathogen, and consequently that having the molecular diagnostic results would bolster clinicians’ prescribing confidence. Molecular Diagnostic Concerns included unfamiliarity with the device’s capabilities, worry that it would detect non-pathogenic bacteria, uncertainty whether it would fail to detect pathogens, and discomfort with withholding antibiotics until receiving molecular test results. Conclusions Clinicians believed rapid molecular diagnostics for pneumonias were potentially important and were open to using them; however, they harboured concerns about the tests’ capabilities and integration into clinical practice. Implementation strategies should bolster users’ necessity beliefs while reducing their concerns; this can be accomplished by publicising the tests’ purpose and benefits, identifying and addressing clinicians’ misconceptions, establishing a trial period for first-hand familiarisation, and emphasising that, with a swift (e.g., 60–90 min) test, antibiotics can be started and refined after molecular diagnostic results become available.

Rationale Upper limb dysfunction is well recognised in survivors of intensive care (Gustafson et al Crit Care Med 2018;46:1769-1774). A mainstay of respiratory support through the COVID-19 pandemic has been use of repeated patient prone positioning to improve ventilation. Potential complications reported with prone positioning of sedated patients include brachial plexopathy, shoulder subluxation and peripheral nerve injury. We hypothesised that there would be a high prevalence of upper limb dysfunction, disability and pain in survivors of COVID-19 requiring mechanical ventilation, particularly in those who were prone positioned. Methods Eligible patients were laboratory-confirmed swab positive for SARS-CoV-2, mechanically ventilated for a minimum of 72 hours on the Royal Brompton Hospital Adult Intensive Care Units. We measured handgrip strength (HGS), normalised for age and sex, the Disability of Arm Shoulder Hand (DASH) questionnaire (Beaton et al J Hand Ther 2001;14:128-146) and Upper limb Pain Numerical Rating Scale (from 0-10). Health related quality of life was measured using the EuroQol-5 dimensions 5-level (EQ5D5L Utility Index (UI) and Visual Analogue Score (VAS)). Patients were stratified according to whether they received prone positioning or not. Results Twenty-seven consecutive patients were assessed at mean 45 days after hospital discharge. Baseline demographics, admission characteristics, and follow-up upper limb assessment data are shown in Table 1. There was evidence of upper limb weakness (mean (SD) right HGS: 44.77(19.31) %predicted;left HGS 47.69 (18.41) %predicted), with 63% showing upper limb dysfunction (DASH ≥ 16) and 33% showing severe upper limb dysfunction (DASH ≥40). Median (IQR) pain scores were 4 (0.75-6.25) with 53% reporting severe pain (≥ 5). DASH correlated significantly with EQ5D5L UI and VAS (r=-0.69 and r=-0.73 respectively;both p

ObjectivesTo conduct an independent study investigating how adults perceive the usability, and functionality of the “NHS COVID-19” app. This study aims to highlight strengths, and provide recommendations to improve adoption of future contact tracing developments.DesignA 60-item, anonymous online questionnaire, disseminated through social media outlets and email-lists by a team from Imperial College London.SettingEnglandParticipantsConvenience sample of 1036 responses, from participants aged 18 and above, between December 2020 to February 2021.Primary Outcome MeasuresEvaluate the compliance and public attitude towards the “NHS COVID-19” app, regarding its functionality and features. This included whether participants expectations were met, and their thoughts on the app privacy and security. Furthermore, to distinguish how usability, perception, and adoption differed with varying demographics and user values.ResultsFair app compliance was identified, with the app meeting expectations of 62.1% of participants who stated they downloaded it after weighted analysis. However, participants finding the interface challenging were less likely to read information in the app and had a lesser understanding of its functionality. Furthermore, lack of understanding regarding the app’s functionality and privacy concerns were possibly reasons why users did not download it. A readability analysis of the text revealed that app information was conveyed at a level which might only be accessible to under 60% of the population. The study highlighted issues related to the potential of false positives caused by the design choices in the “Check-In” feature.ConclusionThis study showed that while the “NHS COVID-19” app was viewed positively, there remained issues regarding participants’ perceived knowledge of the app functionality, potentially affecting compliance. Therefore, we recommended improvements regarding the delivery and presentation of the app’s information, and highlighted the potential need for the ability to check out of venues to reduce the number of false positive contacts.Strengths and LimitationsThis is the first study assessing the perceived usability and functionality of the “NHS COVID-19” app directly from app users.Diverse sample size, with representation from all major regions of England.Statistical analysis to compare perceived app usability and functionality across demographics and the participants values regarding privacy and information.Study was conducted during lockdown where app use may have been minimal.Study may have missed potential participants who were not active on the relevant social media channels and email mailing lists which were used to disseminate the survey.

Background Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. Methods Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p Results Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16–24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. Conclusion Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. Trial registration: The study was registered with Clinical trials.gov Identifier: NCT04534569.

Introduction COVID-19 mortality rates are high, particularly in patients requiring invasive ventilatory support, developing a cytokine storm, or experiencing thromboembolic disease Our goal was to determine if traffic-light driven, personalised care was associated with improved survival in acute hospital settings Methods Outcomes were evaluated during two implementation phases of a real-time clinical decision support tool that had been developed as part of a Trust's COVID-19 response, using a reporting and bioinformatics team to support Clinical and Operational teams Following optimisation, the tool defined patients' clinical status in terms of risk of preventable complications based on blood test results (Ddimer, C reactive protein and ferritin) Feedback to wardbased clinicians enabled rapid modification of care pathways, in the first phase following a daily review, and in the second phase, in real-time (dashboard updated every 10 minutes) Results 1039 COVID-19 positive patients were admitted by 21/05/2020 Focusing on the first 939 completed encounters to death or home discharge (median age 69ys;60% [563/939] male), 568/939 (60 4%) received thromboembolism risk flags, and 212/939 (22 5%) cytokine storm flags The maximum thromboembolism flag discriminated completed encounter mortality between no flag (9 97% [37/371]);medium-risk (28 5% [68/239]);high-risk (51 2% [105/205]);and suspected thromboembolism (52 4% [65/124]), Kruskal Wallis p

Background Corona Virus Disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure carries a high mortality. Coagulopathy has emerged as a significant contributor to thrombotic complications. Case summary We describe two cases of severe COVID-19 pneumonitis refractory to conventional mechanical ventilation and proning position, transferred to our specialist centre for cardiorespiratory failure. Cross-sectional imaging demonstrated concurrent venous and aortic thrombosis with end-organ ischaemic changes. One patient received thrombolysis with a partial response. This could not be offered to the other patient due to a recent haemorrhagic event. Both patients died of multi-organ failure in the hospital. Discussion Concurrent aortic and venous thromboses are rare. This finding in COVID-19 cases, who were both critically ill patients, likely reflects the strongly thrombogenic nature of this illness which ultimately contributed to poor outcomes. The absence of deep vein thrombosis or a potential systemic source of embolism suggests in situ thrombosis. Further, the management of anticoagulation and thrombolysis is challenging in patients where an attendant bleeding risk exists.

Despite advances in the pathophysiology of chronic obstructive pulmonary disease (COPD), there is a distinct lack of biochemical markers to aid clinical management. Microvesicles (MVs) have been implicated in the pathophysiology of inflammatory diseases including COPD, but their association to COPD disease severity remains unknown. We analyzed different MV populations in plasma and bronchoalveolar lavage fluid (BALF) taken from 62 patients with mild to very severe COPD (51% male; mean age: 65.9 yr). These patients underwent comprehensive clinical evaluation (symptom scores, lung function, and exercise testing), and the capacity of MVs to be clinical markers of disease severity was assessed. We successfully identified various MV subtype populations within BALF [leukocyte, polymorphonuclear leukocyte (PMN; i.e., neutrophil), monocyte, epithelial, and platelet MVs] and plasma (leukocyte, PMN, monocyte, and endothelial MVs) and compared each MV population to disease severity. BALF neutrophil MVs were the only population to significantly correlate with the clinical evaluation scores including forced expiratory volume in 1 s, modified Medical Research Council dyspnea score, 6-min walk test, hyperinflation, and gas transfer. BALF neutrophil MVs, but not neutrophil cell numbers, also strongly correlated with BODE index. We have undertaken, for the first time, a comprehensive evaluation of MV profiles within BALF/plasma of COPD patients. We demonstrate that BALF levels of neutrophil-derived MVs are unique in correlating with a number of key functional and clinically relevant disease severity indexes. Our results show the potential of BALF neutrophil MVs for a COPD biomarker that tightly links a key pathophysiological mechanism of COPD (intra-alveolar neutrophil activation) with clinical severity/outcome.

Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) provides a bridge to recovery in patients with acute respiratory failure due to the acute respiratory distress syndrome (ARDS). Survival in ARDS has improved over 15 years, and VV-ECMO may rescue even the most severe of these patients. Predictors of survival on ICU are based upon the principles of reversibility of the inciting aetiology, and premorbid 'reserve' - an imprecise term encompassing comorbidities and frailty. ECMO can support failing organs for prolonged periods, thus sometimes masking trajectories of decline, or unmasking irretrievable intrinsic conditions at a later time point in the critical illness. Clinicians are confronted with new on-treatment dilemmas: how long should we continue this high level of care? Will the patient's limited respiratory reserve manage off ECMO? Or are we hastening their demise? How long is it justifiable to keep someone on ECMO, if the predicted survival off is ultimately poor, but they are in a stable state whilst supported? The palliative withdrawal from ECMO is unchartered territory that requires further study. We describe two representative cases and discuss the wide ethical issues surrounding the initiation and withdrawal of ECMO. ispartof: ACTA CARDIOLOGICA vol:76 issue:5 pages:455-458 ispartof: location:England status: published

Common causes of death in COVID-19 due to SARS-CoV-2 include thromboembolic disease, cytokine storm and adult respiratory distress syndrome (ARDS). Our aim was to develop a system for early detection of disease pattern in the emergency department (ED) that would enhance opportunities for personalised accelerated care to prevent disease progression. A single Trust’s COVID-19 response control command was established, and a reporting team with bioinformaticians was deployed to develop a real-time traffic light system to support clinical and operational teams. An attempt was made to identify predictive elements for thromboembolism, cytokine storm and ARDS based on physiological measurements and blood tests, and to communicate to clinicians managing the patient, initially via single consultants. The input variables were age, sex, and first recorded blood pressure, respiratory rate, temperature, heart rate, indices of oxygenation and C-reactive protein. Early admissions were used to refine the predictors used in the traffic lights. Of 923 consecutive patients who tested COVID-19 positive, 592 (64%) flagged at risk for thromboembolism, 241/923 (26%) for cytokine storm and 361/923 (39%) for ARDS. Thromboembolism and cytokine storm flags were met in the ED for 342 (37.1%) patients. Of the 318 (34.5%) patients receiving thromboembolism flags, 49 (5.3% of all patients) were for suspected thromboembolism, 103 (11.1%) were high-risk and 166 (18.0%) were medium-risk. Of the 89 (9.6%) who received a cytokine storm flag from the ED, 18 (2.0% of all patients) were for suspected cytokine storm, 13 (1.4%) were high-risk and 58 (6.3%) were medium-risk. Males were more likely to receive a specific traffic light flag. In conclusion, ED predictors were used to identify high proportions of COVID-19 admissions at risk of clinical deterioration due to severity of disease, enabling accelerated care targeted to those more likely to benefit. Larger prospective studies are encouraged.

IntroductionAutomated systems for ventilator management to date have been either fully heuristic rule-based systems or based on a combination of simple physiological models and rules. These have been shown to reduce the duration of mechanical ventilation in simple to wean patients. At present, there are no published studies that evaluate the effect of systems that use detailed physiological descriptions of the individual patient.The BEACON Caresystem is a model-based decision support system that uses mathematical models of patients’ physiology in combination with models of clinical preferences to provide advice on appropriate ventilator settings. An individual physiological description may be particularly advantageous in selecting the appropriate therapy for a complex, heterogeneous, intensive care unit (ICU) patient population.Methods and analysisIntenive Care weaning (iCareWean) is a single-blinded, multicentre, prospective randomised control trial evaluating management of mechanical ventilation as directed by the BEACON Caresystem compared with that of current care, in the general intensive care setting. The trial will enrol 274 participants across multiple London National Health Service ICUs. The trial will use a primary outcome of duration of mechanical ventilation until successful extubation.Ethics and disseminationSafety oversight will be under the direction of an independent committee of the study sponsor. Study approval was obtained from the regional ethics committee of the Health Research Authority (HRA), (Research Ethic Committee (REC) reference: 17/LO/0887. Integrated Research Application System (IRAS) reference: 226610. Results will be disseminated through international critical care conference/symposium and publication in peer-reviewed journal.Trial registration numberClinicalTrials.gov under NCT03249623. This research is registered with the National Institute for Health Research under CPMS ID: 34831.

Studies conducted in people living with HIV (PLHIV) report high rates of sleep disturbance, without a clear explanation as to cause or effect. Therefore, we proposed use of multiple validated questionnaires that would allow a more comprehensive evaluation of sleep quality in PLHIV. We administered eight validated sleep and wellbeing questionnaires, recording different aspects of sleep in order to provide a comprehensive description of sleep quality, quantity, daytime functioning, wakefulness, and general wellbeing. Associations with demographics and clinical data were analyzed by univariable/multivariable analyses. Of 254 subjects 99% were male (98% men who have sex with men), 88% white, mean age 41 (SD ± 9.9) years, HIV duration eight years (SD ± 6.3), 94% were on antiretroviral therapy, mean CD4 cell count was 724 cells/mm3, 81% had HIV RNA