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Abstract Background Throughout the Covid-19 pandemic, researchers have made use of electronic health records to research this disease in a rapidly evolving environment of questions and discoveries. These studies are prone to collider bias as they restrict the population of Covid-19 patients to only those with severe disease. Inverse probability weighting is typically used to correct for this bias but requires information from the unrestricted population. Using electronic health records from a South London NHS trust, this work demonstrates a method to correct for collider bias using externally sourced data while examining the relationship between minority ethnicities and poor Covid-19 outcomes. Methods The probability of inclusion within the observed hospitalised cohort was modelled based on estimates from published national data. The model described the relationship between patient ethnicity, hospitalisation, and death due to Covid-19 – a relationship suggested to be susceptible to collider bias. The obtained probabilities (as applied to the observed patient cohort) were used as inverse probability weights in survival analysis examining ethnicity (and covariates) as a risk factor for death due to Covid-19. Results Within the observed cohort, unweighted analysis of survival suggested a reduced risk of death in those of Black ethnicity – differing from the published literature. Applying inverse probability weights to this analysis amended this aberrant result to one more compatible with the literature. This effect was consistent when the analysis was applied to patients within only the first wave of Covid-19 and across two waves of Covid-19 and was robust against adjustments to the modelled relationship between hospitalisation, patient ethnicity, and death due to Covid-19 made as part of a sensitivity analysis. Conclusions In conclusion, this analysis demonstrates the feasibility of using external publications to correct for collider bias (or other forms of selection bias) induced by the restriction of a population to a hospitalised cohort using an example from the recent Covid-19 pandemic.

Abstract Background Acute skeletal muscle wasting during critical illness is common and causes significant morbidity and functional limitation. Myofibre necrosis is a major histological finding but is often considered an unprogrammed by‐product of muscle inflammation. This study sought to evaluate if a form of programmed necrosis, necroptosis, is activated in skeletal muscle during critical illness. Methods A cohort of 28 patients from the MUSCLE‐UK study (ClinicalTrials.gov: NCT01106300) with serum and skeletal muscle biopsy samples were identified. Samples were available from ICU admission (T1) and between day 7–10 post admission (T2). Skeletal muscle was stratified by a histopathologist in the original study as necrotic (NEC, N = 14) or non‐necrotic (NONEC, N = 14) using haematoxylin and eosin staining. We used phosphorylated mixed‐lineage kinase domain‐like (pMLKL) protein (a key terminal effector protein) and receptor‐interacting protein kinase 3 (RIPK3) as markers of necroptosis activation using Western blotting and immunohistochemistry. Results We show that pMLKL expression is significantly higher in the NEC group [NEC: T2:T1 expression; 9.1 (IQR 3.9–22.3) vs. NONEC: T2:T1 expression; 0.9 (IQR 0.6–1.1), P = 0.003]. We then confirm this upregulation and describe co‐localization with receptor interacting protein kinase 3 (RIPK3) in skeletal muscle using immunohistochemistry. We show that both RIPK3 and pMLKL are present within intact myofibres at the intermediate timepoint day 3 without cellular infiltrate. At T2, pMLKL is also present in the interstitial space where there is infiltrate of CD68 positive immune cells. The observed necroptosis may originate from both internal and infiltrating sources. These findings were absent in samples from patients who did not exhibit histopathological features of necrosis. Conclusions We show that necroptosis machinery, RIPK3 and pMLKL, are associated with conventional histopathological features of myonecrosis in a critically ill cohort.

Objective Identify prevalence of self-reported swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19.Design Multicentre prospective observational cohort study using questionnaire data at visit 1 (2–7 months post discharge) and visit 2 (10–14 months post discharge) from hospitalised patients in the UK. Lasso logistic regression analysis was undertaken to identify associations.Setting 64 UK acute hospital Trusts.Participants Adults aged >18 years, discharged from an admissions unit or ward at a UK hospital with COVID-19.Main outcome measures Self-reported swallow, communication, voice and cognitive compromise.Results Compromised swallowing post intensive care unit (post-ICU) admission was reported in 20% (188/955); 60% with swallow problems received invasive mechanical ventilation and were more likely to have undergone proning (p=0.039). Voice problems were reported in 34% (319/946) post-ICU admission who were more likely to have received invasive (p

Home mechanical ventilation (HMV) is a treatment for chronic respiratory failure that has shown clinical and cost effectiveness in patients with underlying COPD, obesity-related respiratory failure and neuromuscular disease (NMD). By treating chronic respiratory failure with adequate adherence to HMV, improvement in patient-reported outcomes including health-related quality of life (HRQoL) have been evaluated using general and disease-specific quantitative, semi-qualitative and qualitative methods. However, the treatment response in terms of trajectory of change in HRQoL is not uniform across the restrictive and obstructive disease groups. In this review, the effect of HMV on HRQoL across the domains of symptom perception, physical wellbeing, mental wellbeing, anxiety, depression, self-efficacy and sleep quality in stable and post-acute COPD, rapidly progressive NMD (such as amyotrophic lateral sclerosis), inherited NMD (including Duchenne muscular dystrophy) and obesity-related respiratory failure will be discussed.

Background: There are limited data reporting diagnostic practices, compared to clinical guidelines, for patients with chronic respiratory failure requiring home mechanical ventilation (HMV). There are no data detailing the current use of downloaded physiological monitoring data in day-to-day clinical practice during initiation and follow up of patients on HMV. This survey reports clinicians’ practices, with a specific focus on the clinical approaches employed to assess, monitor and manage HMV patients. Methods: A web-based international survey was open between 1 January and 31 March 2023. Results: In total, 114 clinicians responded; 84% of the clinicians downloaded the internal physiological ventilator data when initiating and maintaining HMV patients, and 99% of the clinicians followed up with patients within 3 months. Adherence, leak and the apnea-hypopnea index were the three highest rated items. Oxygen saturation was used to support a diagnosis of nocturnal hypoventilation and was preferred over measurements of carbon dioxide. Furthermore, 78% of the clinicians reviewed data for the assessment of patient ventilator asynchrony (PVA), although the confidence reported in identifying certain PVAs was reported as unconfident or extremely unconfident. Conclusions: This survey confirmed that clinical practice varies and often does not follow the current guidelines. Despite PVA being of clinical interest, its clinical relevance was not clear, and further research, education and training are required to improve clinical confidence.

Abstract Background Patients presenting with acute hypercapnic respiratory failure due to exacerbations of chronic obstructive pulmonary disease (AECOPD) are typically managed with non-invasive ventilation (NIV). The impact of low-flow extracorporeal carbon dioxide removal (ECCO2R) on outcome in these patients has not been explored in randomised trials. Methods Open-label randomised trial comparing NIV (NIV arm) with ECCO2R (ECCO2R arm) in patients with AECOPD at high risk of NIV failure (pH

Background Inhaled corticosteroids (ICS) are frequently prescribed outside guidelines to patients with chronic obstructive pulmonary disease (COPD) with mild/moderate airflow limitation and low exacerbation risk. This primary care trial explored the feasibility of identifying patients with mild/moderate COPD taking ICS, and the acceptability of ICS withdrawal.Methods Open feasibility trial. Outcome measures included prevalence of suitable participants, feasibility of their identification, their willingness-to-accept open randomisation to ICS withdrawal or continuation over 6 months follow-up.Results 392 (13%) of 2967 patients with COPD from 20 practices (209 618 population) identified as eligible for ICS withdrawal by electronic search algorithm. After individual patient record review, 243 (62%) were excluded because of: severe airflow limitation (65, 17%); one or more severe or two or more moderate COPD exacerbations in the previous year (86, 22%); asthma (15, 4%); and severe comorbidities (77, 20%). After exclusion, 149 patients with COPD were invited to participate and 61 agreed to randomisation. At clinical assessment, 10 patients exhibited undocumented airflow reversibility (forced expiratory volume in 1 s (FEV1) reversibility >12% and >200 mL); 2 had suffered two or more undocumented, moderate exacerbations in the previous year; 7 had severe airflow limitation; and 2 had normal spirometry. Finally, 40 were randomised. One patient died and one was lost to follow-up. 18 (45%) of the 38 (10 withdrawal and 8 usual care) exhibited previously undocumented FEV1 variability suggestive of asthma, supported in the withdrawal group by significant associations with elevated fractional exhaled nitric oxide (p=0.04), elevated symptom score (p=0.04), poorer quality of life (p=0.04) and atopic status (p=0.01).Conclusions Identifying primary care patients with mild/moderate COPD suitable for ICS withdrawal is feasible but requires real-time verification because of unreliable recording of exacerbations and lung function. Suitable patients accepted randomisation to ICS withdrawal or continuation for the purposes of future studies. Follow-up compliance was high. Nearly 50% of participants with a diagnosis of mild/moderate COPD demonstrated previously undocumented FEV1 variability during follow-up, mandating monitoring for at least 6 months following withdrawal to exclude undiagnosed asthma.

Introduction Physical rehabilitation delivered early following admission to the intensive care unit (ICU) has the potential to improve short-term and long-term outcomes. The use of supine cycling together with other rehabilitation techniques has potential as a method of introducing rehabilitation earlier in the patient journey. The aim of the study is to determine the feasibility of delivering the designed protocol of a randomised clinical trial comparing a protocolised early rehabilitation programme including cycling with usual care. This feasibility study will inform a larger multicentre study.Methods and analysis 90 acute care medical patients from two mixed medical–surgical ICUs will be recruited. We will include ventilated patients within 72 hours of initiation of mechanical ventilation and expected to be ventilated a further 48 hours or more. Patients will receive usual care or usual care plus two 30 min rehabilitation sessions 5 days/week.Feasibility outcomes are (1) recruitment of one to two patients per month per site; (2) protocol fidelity with >75% of patients commencing interventions within 72 hours of mechanical ventilation, with >70% interventions delivered; and (3) blinded outcome measures recorded at three time points in >80% of patients. Secondary outcomes are (1) strength and function, the Physical Function ICU Test–scored measured on ICU discharge; (2) hospital length of stay; and (3) mental health and physical ability at 3 months using the WHO Disability Assessment Schedule 2. An economic analysis using hospital health services data reported with an embedded health economic study will collect and assess economic and quality of life data including the Hospital Anxiety and Depression Scales core, the Euroqol-5 Dimension-5 Level and the Impact of Event Score.Ethics and dissemination The study has ethical approval from the South Central Hampshire A Research Ethics Committee (19/SC/0016). All amendments will be approved by this committee. An independent trial monitoring committee is overseeing the study. Results will be made available to critical care survivors, their caregivers, the critical care societies and other researchers.Trial registration number NCT03771014.

Abstract Background Increasing numbers of critically ill patients experience a prolonged intensive care unit stay contributing to greater physical and psychological morbidity, strain on families and cost to health systems. Quality improvement tools such as checklists concisely articulate best practices with the aim of improving quality and safety; however, these tools have not been designed for the specific needs of patients with prolonged ICU stay. The primary objective of this review will be to determine the characteristics including format and content of multicomponent tools designed to standardise or improve ICU care. Secondary objectives are to describe the outcomes reported in these tools, the type of patients and settings studied, and to understand how these tools were developed and implemented in clinical practice. Methods We will search the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, MEDLINE, PsycINFO, Web of Science, OpenGrey, NHS evidence and Trial Registries from January 2000 onwards. We will include primary research studies (e.g. experimental, quasi-experimental, observational and qualitative studies) recruiting more than 10 adult participants admitted to ICUs, high dependency units and weaning centres regardless of length of stay, describing quality improvement tools such as structured care plans or checklists designed to standardize more than one aspect of care delivery. We will extract data on study and patient characteristics, tool design and implementation strategies and measured outcomes. Two reviewers will independently screen citations for eligible studies and perform data extraction. Data will be synthesised with descriptive statistics; we will use a narrative synthesis to describe review findings. Discussion The findings will be used to guide development of tools for use with prolonged ICU stay patients. Our group will use experience-based co-design methods to identify the most important actionable processes of care to include in quality improvement tools these patients. Such tools are needed to standardise practice and thereby improve quality of care. Illustrating the development and implementation methods used for such tools will help to guide translation of similar tools into ICU clinical practice and future research. Systematic review registration This protocol is registered on the Open Science Framework, https://osf.io/ , DOI https://doi.org/10.17605/OSF.IO/Z8MRE

Abstract Background The clinical effectiveness of neurally adjusted ventilatory assist (NAVA) has yet to be demonstrated, and preliminary studies are required. The study aim was to assess the feasibility of a randomized controlled trial (RCT) of NAVA versus pressure support ventilation (PSV) in critically ill adults at risk of prolonged mechanical ventilation (MV). Methods An open-label, parallel, feasibility RCT (n = 78) in four ICUs of one university-affiliated hospital. The primary outcome was mode adherence (percentage of time adherent to assigned mode), and protocol compliance (binary—≥ 65% mode adherence). Secondary exploratory outcomes included ventilator-free days (VFDs), sedation, and mortality. Results In the 72 participants who commenced weaning, median (95% CI) mode adherence was 83.1% (64.0–97.1%) and 100% (100–100%), and protocol compliance was 66.7% (50.3–80.0%) and 100% (89.0–100.0%) in the NAVA and PSV groups respectively. Secondary outcomes indicated more VFDs to D28 (median difference 3.0 days, 95% CI 0.0–11.0; p = 0.04) and fewer in-hospital deaths (relative risk 0.5, 95% CI 0.2–0.9; p = 0.032) for NAVA. Although overall sedation was similar, Richmond Agitation and Sedation Scale (RASS) scores were closer to zero in NAVA compared to PSV (p = 0.020). No significant differences were observed in duration of MV, ICU or hospital stay, or ICU, D28, and D90 mortality. Conclusions This feasibility trial demonstrated good adherence to assigned ventilation mode and the ability to meet a priori protocol compliance criteria. Exploratory outcomes suggest some clinical benefit for NAVA compared to PSV. Clinical effectiveness trials of NAVA are potentially feasible and warranted. Trial registration ClinicalTrials.gov , NCT01826890 . Registered 9 April 2013.

Background: Patient-ventilator synchronization during non-invasive ventilation (NIV) can be assessed by visual inspection of flow and pressure waveforms but it remains time consuming and there is a large inter-rater variability, even among expert physicians. SyncSmart™ software developed by Breas Medical (Mölnycke, Sweden) provides an automatic detection and scoring of patient-ventilator asynchrony to help physicians in their daily clinical practice. This study was designed to assess performance of the automatic scoring by the SyncSmart software using expert clinicians as a reference in patient with chronic respiratory failure receiving NIV.Methods: From nine patients, 20 min data sets were analyzed automatically by SyncSmart software and reviewed by nine expert physicians who were asked to score auto-triggering (AT), double-triggering (DT), and ineffective efforts (IE). The study procedure was similar to the one commonly used for validating the automatic sleep scoring technique. For each patient, the asynchrony index was computed by automatic scoring and each expert, respectively. Considering successively each expert scoring as a reference, sensitivity, specificity, positive predictive value (PPV), κ-coefficients, and agreement were calculated.Results: The asynchrony index assessed by SynSmart was not significantly different from the one assessed by the experts (18.9 ± 17.7 vs. 12.8 ± 9.4, p = 0.19). When compared to an expert, the sensitivity and specificity provided by SyncSmart for DT, AT, and IE were significantly greater than those provided by an expert when compared to another expert.Conclusions:SyncSmart software is able to score asynchrony events within the inter-rater variability. When the breathing frequency is not too high (

Abstract Objective The trial objective is to determine if Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) is clinically effective compared to standard oxygen therapy in patients with confirmed or suspected COVID-19. Trial design Adaptive (group-sequential), parallel group, pragmatic, superiority randomised controlled, open-label, multi-centre, effectiveness trial. Participants The trial is being conducted across approximately 60 hospitals across England, Wales, Scotland, and Northern Ireland. Inpatients at participating hospitals are eligible to participate if they have respiratory failure with suspected or proven COVID-19, and meet all of the inclusion criteria and none of the exclusion criteria. Inclusion criteria: 1) Adults ≥ 18 years; 2) Admitted to hospital with suspected or proven COVID-19; 3) Receiving oxygen with fraction of inspired oxygen (FiO2) ≥0.4 and peripheral oxygen saturation (SpO2) ≤94%; and 4) Plan for escalation to tracheal intubation if needed. Exclusion criteria: 1) Planned tracheal intubation and mechanical ventilation imminent within 1 hour; 2) Known or clinically apparent pregnancy; 3) Any absolute contraindication to CPAP or HFNO; 4) Decision not to intubate due to ceiling of treatment or withdrawal of treatment anticipated; and 5) Equipment for both CPAP and HFNO not available. Intervention and comparator Intervention one: Continuous positive airway pressure delivered by any device. Set-up and therapy titration is not protocolised and is delivered in accordance with clinical discretion. Intervention two: High-flow nasal oxygen delivered by any device. Set-up and therapy titration is not protocolised and is delivered in accordance with clinical discretion. Comparator group: Standard care- oxygen delivered by face mask or nasal cannula (excluding the use of continuous positive airway pressure or high-flow nasal oxygen). Set-up and therapy titration is not protocolised and is delivered in accordance with clinical discretion. Intervention delivery continues up to the point of death, tracheal intubation, or clinical determination that there is no ongoing need (palliation or improvement). Main outcomes The primary outcome is a composite outcome comprising tracheal intubation or mortality within 30 days following randomisation. Secondary outcomes include tracheal intubation rate, time to tracheal intubation, duration of invasive ventilation, mortality rate, time to mortality, length of hospital stay, and length of critical care stay. Randomisation Participants are randomised in a 1:1:1 ratio to receive either continuous positive airway pressure, high-flow nasal oxygen or standard care. Due to the challenging environment of study delivery, a specific intervention may not always be available at the hospital site. The study uses two integrated randomisation systems to allow, where required, the site to randomise between all three interventions, between CPAP and standard care, and between HFNO and standard care. System integration ensures maintenance of balance between interventions. Randomisation is performed using a telephone-based interactive voice response system to maintain allocation concealment. The randomisation sequence was computer-generated using the minimisation method. Participant randomisation is stratified by site, gender (M/F), and age (=50 years). Blinding (masking) The nature of the trial interventions precludes blinding of the researcher, patient and clinical team. Primary and secondary outcomes are all objective outcomes, thereby minimising the risk of detection bias. Numbers to be randomised (sample size) 4002 participants (1334 to be randomized to each of the three study arms) Trial Status Current protocol: Version 4.0, 29th May 2020. Recruitment began on April 6, 2020 and is anticipated to be complete by April 5, 2021. The trial has been awarded Urgent Public Health status by the National Institute of Health Research on 13th April 2020. Trial registration ISRCTN, ISRCTN16912075. Registered 6th April 2020, http://www.isrctn.com/ISRCTN16912075 Full protocol The full protocol (version 4.0, 29th May 2020) 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Abstract Background Chronic obstructive pulmonary disease (COPD) is a common cause of chronic respiratory failure and its course is punctuated by a series of acute exacerbations which commonly lead to hospital admission. Exacerbations are managed through the application of non-invasive ventilation and, when this fails, tracheal intubation and mechanical ventilation. The need for mechanical ventilation significantly increases the risk of death. An alternative therapy, extracorporeal carbon dioxide removal (ECCO2R), has been shown to be efficacious in removing carbon dioxide from the blood; however, its impact on respiratory physiology and patient outcomes has not been explored. Methods/design A randomised controlled open label trial of patients (12 in each arm) with acute exacerbations of COPD at risk of failing conventional therapy (NIV) randomised to either remaining on NIV or having ECCO2R added to NIV with a primary endpoint of time to cessation of NIV. The change in respiratory physiology following the application of ECCO2R and/or NIV will be measured using electrical impedance tomography, oesophageal pressure and parasternal electromyography. Additional outcomes, including patient tolerance, outcomes, need for readmission, changes in blood gases and biochemistry and procedural complications, will be measured. Physiological changes will be compared within one patient over time and between the two groups. Healthcare costs in the UK system will also be compared between the two groups. Discussion COPD is a common disease and exacerbations are a leading cause of hospital admission in the UK and worldwide, with a sizeable mortality. The management of patients with COPD consumes significant hospital and financial resources. This study seeks to understand the feasibility of a novel approach to the management of patients with acute exacerbations of COPD as well as to understand the underlying physiological changes to explain why the approach does or does not assist this patient cohort. Detailed respiratory physiology has not been previously undertaken using this technique and there are no other randomised controlled trials currently in the literature. Trial registration ClinicalTrials.gov, NCT02086084.

Abstract Design This randomised crossover trial compared nocturnal auto-adjusting continuous positive airway pressure (APAP) and nocturnal oxygen therapy (NOT) in adults and children with sickle cell anaemia, with patient acceptability as the primary outcome. Secondary outcomes included pulmonary physiology (adults), safety, and daily pain during interventions and washout documented using tablet technology. Methods Inclusion criteria were age > 8 years and the ability to use an iPad to collect daily pain data. Trial participation was 4 weeks; week 1 involved baseline data collection and week 3 was a washout between interventions, which were administered for 7 days each during weeks 2 and 4 in a randomised order. Qualitative interviews were transcribed verbatim and analysed for content using a funnelling technique, starting generally and then gaining more detailed information on the experience of both interventions. Safety data included routine haematology and median pain days between each period. Missing pain day values were replaced using multiple imputation. Results Ten adults (three female, median age 30.2 years, range 18–51.5 years) and eleven children (five female, median age 12 years, range 8.7–16.9 years) enrolled. Nine adults and seven children completed interviews. Qualitative data revealed that the APAP machine was smaller, easier to handle, and less noisy. Of 16 participants, 10 preferred APAP (62.5%, 95% confidence interval (CI) 38.6–81.5%). Haemoglobin decreased from baseline on APAP and NOT (mean difference −3.2 g/L (95% CI −6.0 to −0.2 g/L) and −2.5 g/L (95% CI −4.6 to 0.3 g/L), respectively), but there was no significant difference between interventions (NOT versus APAP, 1.1 (−1.2 to 3.6)). Pulmonary function changed little. Compared with baseline, there were significant decreases in the median number of pain days (1.58 for APAP and 1.71 for NOT) but no significant difference comparing washout with baseline. After adjustment for carry-over and period effects, there was a non-significant median difference of 0.143 (95% CI −0.116 to 0.401) days additional pain with APAP compared with NOT. Conclusion In view of the point estimate of patient preference for APAP, and no difference in haematology or pulmonary function or evidence that pain was worse during or in washout after APAP, it was decided to proceed with a Phase II trial of 6 months APAP versus standard care with further safety monitoring for bone marrow suppression and pain. Trial registration ISRCTN46078697. Registered on 18 July 2014

Introduction Relapsing polychondritis is a rare multisystem vasculitis characterised by recurrent cartilage inflammation. Respiratory involvement, of which tracheobronchomalacia (TBM) is the commonest form, is difficult to treat and is linked to increased mortality. We describe 13 patients with respiratory involvement. Methods This is a retrospective study of all the patients with relapsing polychondritis at University Hospitals Coventry and Warwickshire NHS Trust (UHCW), a secondary care provider for ∼500 000. Only patients with respiratory involvement were included in this study. Results We identified 13 patients who fulfilled the inclusion criteria. Most patients were identified from the “difficult asthma” clinic. TBM was seen in 11 patients, whilst two patients had pleural effusions which resolved with immunosuppression and one patient had small airways disease. Computed tomography scans (inspiratory and expiratory) and bronchoscopy findings were useful in diagnosing TBM. Pulmonary function testing revealed significant expiratory flow abnormalities. All patients were treated with corticosteroids/disease-modifying anti-rheumatic drugs (DMARDs) and some were given cyclophosphamide or biological agents, although the response to cyclophosphamide (1 out of 4) or biologicals (2 out of 4) was modest in this cohort. Ambulatory continuous positive airway pressure ventilation was successful in four patients. Conclusions Relapsing polychondritis may be overlooked in “difficult asthma” clinics with patients having TBM (not asthma) and other features of relapsing polychondritis. Awareness of this condition is crucial to enable early diagnosis and interventions to reduce the risk of life-threatening airway collapse. A number of patients respond well to DMARDs and are able to minimise corticosteroid use.

Humidified high-flow therapy (HFT) is a noninvasive respiratory therapy, typically delivered through a nasal cannula interface, which delivers a stable fraction of inspired oxygen (FIO2) at flow rates of up to 60 L·min−1. It is well-tolerated, simple to set up and ideally applied at 37°C to permit optimal humidification of inspired gas. Flow rate and FIO2 should be selected based on patients' inspiratory effort and severity of hypoxaemia. HFT yields beneficial physiological effects, including improved mucociliary clearance, enhanced dead space washout and optimisation of pulmonary mechanics. Robust evidence supports its application in the critical care setting (treatment of acute hypoxaemic respiratory failure and prevention of post-extubation respiratory failure) and emerging data supports HFT use during bronchoscopy, intubation and breaks from noninvasive ventilation or continuous positive airway pressure. There are limited data on HFT use in patients with hypercapnic respiratory failure, as an adjunct to pulmonary rehabilitation and in the palliative care setting, and further research is needed to validate the findings of small studies. The COVID-19 pandemic raises questions regarding HFT efficacy in COVID-19-related hypoxaemic respiratory failure and concerns regarding aerosolisation of respiratory droplets. Clinical trials are ongoing and healthcare professionals should implement strict precautions to mitigate the risk of nosocomial transmission. Educational aims Provide a practical guide to HFT setup and delivery. Outline the physiological effects of HFT on the respiratory system. Describe clinical applications of HFT in adult respiratory and critical care medicine and evaluate the supporting evidence. Discuss application of HFT in COVID-19 and aerosolisation of respiratory droplets.

Background Neurally adjusted ventilatory assist (NAVA) involves an intricate interaction between patient, clinician and technology. To improve our understanding of this complex intervention and to inform future trials, this survey aimed to examine clinician attitudes, beliefs and barriers to NAVA use in critically ill adults within an institution with significant NAVA experience.Methods A survey of nurses, doctors and physiotherapists in four Intensive Care Units (ICUs) of one UK university-affiliated hospital (75 NAVA equipped beds). The survey consisted of 39 mixed open and structured questions. The hospital had 8 years of NAVA experience prior to the survey.Results Of 466 distributed questionnaires, 301 (64.6%) were returned from 236 nurses (78.4%), 53 doctors (17.6%) and 12 physiotherapists (4.0%). Overall, 207/294 (70.4%) reported clinical experience. Most agreed that NAVA was safe (136/177, 76.8%) and clinically effective (99/176, 56.3%) and most perceived ‘improved synchrony’, ‘improved comfort’ and ‘monitoring the diaphragm’ to be key advantages of NAVA. ‘Technical issues’ (129/189, 68.3%) and ‘NAVA signal problems’ (94/180, 52.2%) were the most cited clinical disadvantage and cause of mode cross-over to Pressure Support Ventilation (PSV), respectively. Most perceived NAVA to be more difficult to use than PSV (105/174, 60.3%), although results were mixed when compared across different tasks. More participants preferred PSV to NAVA for initiating ventilator weaning (93/171 (54.4%) vs 29/171 (17.0%)). A key barrier to use and a consistent theme throughout was ‘low confidence’ in relation to NAVA use.Conclusions In addition to broad clinician support for NAVA, this survey describes technical concerns, low confidence and a perception of difficulty above that associated with PSV. In this context, high-quality training and usage algorithms are critically important to the design and of future trials, to clinician acceptance and to the clinical implementation and future success of NAVA.

Abstract Background Existing data on physical rehabilitation interventions in critical illness are challenged by outcome heterogeneity that limits data synthesis and translation of research findings into clinical practice. This protocol describes the PRACTICE study to develop a core outcome set (COS) for trials of physical rehabilitation interventions delivered across the continuum of a patient’s recovery from the intensive care unit until reintegration in the community following hospital discharge. Methods Mixed methods will be used including: systematic reviews of quantitative and qualitative literature; qualitative interviews with patients and caregivers; a modified Delphi consensus process with researcher, clinician and patient/caregiver stakeholder groups; and consensus meetings for ratification of findings, resolving uncertainty, or developing an action plan for COS implementation. Discussion The PRACTICE COS will inform relevant stakeholders about important outcomes regarding physical rehabilitation in critical illness, and may enhance the future design and conduct of trials in this area. Trial registration COMET database (www.comet-initiative.org/, Record ID 288, 01/03/13). PROSPERO database (CRD42014008908, CRD42017078549).

Abstract Background In addition to pain, sickle cell anaemia (HbSS) complications include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time oxygen saturation compounded by obstructive sleep apnoea (OSA). In the general population OSA is treated with continuous positive airways pressure (CPAP). The aim of this single-blind, randomised, controlled phase II trial is to compare auto-adjusting CPAP (APAP) with standard care to standard care alone in individuals with HbSS to determine whether the intervention improves attention and processing speed, brain structure, pain and quality of life. Methods/Design Eligibility criteria include: ability to provide informed consent; age > 8 years; diagnosis of HbSS; and mean overnight saturation of 23 years); silent infarction on MRI; minimum overnight oxygen saturation > 90% or

Abstract In this review, we seek to highlight how critical illness and critical care affect longer-term outcomes, to underline the contribution of ICU delirium to cognitive dysfunction several months after ICU discharge, to give new insights into ICU acquired weakness, to emphasize the importance of value-based healthcare, and to delineate the elements of family-centered care. This consensus of 29 also provides a perspective and a research agenda about post-ICU recovery.

Abstract The lack of benefit from randomised controlled trials has resulted in significant controversy regarding the role of nutrition during critical illness in terms of long-term recovery and outcome. Although methodological caveats with a failure to adequately appreciate biological mechanisms may explain these disappointing results, it must be acknowledged that nutritional support during early critical illness, when considered alone, may have limited long-term functional impact. This narrative review focuses specifically on recent clinical trials and evaluates the impact of nutrition during critical illness on long-term physical and functional recovery. Specific focus on the trial design and methodological limitations has been considered in detail. Limitations include delivery of caloric and protein targets, patient heterogeneity, short duration of intervention, inappropriate clinical outcomes and a disregard for baseline nutritional status and nutritional intake in the post-ICU period. With survivorship at the forefront of critical care research, it is imperative that nutrition studies carefully consider biological mechanisms and trial design because these factors can strongly influence outcomes, in particular long-term physical and functional outcome. Failure to do so may lead to inconclusive clinical trials and consequent rejection of the potentially beneficial effects of nutrition interventions during critical illness.

Abstract Background Approximately 5 to 10% of critically ill patients transition from acute critical illness to a state of persistent and in some cases chronic critical illness. These patients have unique and complex needs that require a change in the clinical management plan and overall goals of care to a focus on rehabilitation, symptom relief, discharge planning, and in some cases, end-of-life care. However, existing indicators and measures of care quality, and tools such as checklists, that foster implementation of best practices, may not be sufficiently inclusive in terms of actionable processes of care relevant to these patients. Therefore, the aim of this systematic review is to identify the processes of care, performance measures, quality indicators, and outcomes including reports of patient/family experience described in the current evidence base relevant to patients with persistent or chronic critical illness and their family members. Methods Two authors will independently search from inception to November 2016: MEDLINE, Embase, CINAHL, Web of Science, the Cochrane Library, PROSPERO, the Joanna Briggs Institute and the International Clinical Trials Registry Platform. We will include all study designs except case series/reports of

Background: Invasive mechanical ventilation (IMV) is a life-saving intervention. Following resolution of the condition that necessitated IMV, a spontaneous breathing trial (SBT) is used to determine patient readiness for IMV discontinuation. In patients who fail one or more SBTs, there is uncertainty as to the optimum management strategy. Objective: To evaluate the clinical effectiveness and cost-effectiveness of using non-invasive ventilation (NIV) as an intermediate step in the protocolised weaning of patients from IMV. Design: Pragmatic, open-label, parallel-group randomised controlled trial, with cost-effectiveness analysis. Setting: A total of 51 critical care units across the UK. Participants: Adult intensive care patients who had received IMV for at least 48 hours, who were categorised as ready to wean from ventilation, and who failed a SBT. Interventions: Control group (invasive weaning): patients continued to receive IMV with daily SBTs. A weaning protocol was used to wean pressure support based on the patient’s condition. Intervention group (non-invasive weaning): patients were extubated to NIV. A weaning protocol was used to wean inspiratory positive airway pressure, based on the patient’s condition. Main outcome measures: The primary outcome measure was time to liberation from ventilation. Secondary outcome measures included mortality, duration of IMV, proportion of patients receiving antibiotics for a presumed respiratory infection and health-related quality of life. Results: A total of 364 patients (invasive weaning, n = 182; non-invasive weaning, n = 182) were randomised. Groups were well matched at baseline. There was no difference between the invasive weaning and non-invasive weaning groups in median time to liberation from ventilation {invasive weaning 108 hours [interquartile range (IQR) 57–351 hours] vs. non-invasive weaning 104.3 hours [IQR 34.5–297 hours]; hazard ratio 1.1, 95% confidence interval [CI] 0.89 to 1.39; p = 0.352}. There was also no difference in mortality between groups at any time point. Patients in the non-invasive weaning group had fewer IMV days [invasive weaning 4 days (IQR 2–11 days) vs. non-invasive weaning 1 day (IQR 0–7 days); adjusted mean difference –3.1 days, 95% CI –5.75 to –0.51 days]. In addition, fewer non-invasive weaning patients required antibiotics for a respiratory infection [odds ratio (OR) 0.60, 95% CI 0.41 to 1.00; p = 0.048]. A higher proportion of non-invasive weaning patients required reintubation than those in the invasive weaning group (OR 2.00, 95% CI 1.27 to 3.24). The within-trial economic evaluation showed that NIV was associated with a lower net cost and a higher net effect, and was dominant in health economic terms. The probability that NIV was cost-effective was estimated at 0.58 at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year. Conclusions: A protocolised non-invasive weaning strategy did not reduce time to liberation from ventilation. However, patients who underwent non-invasive weaning had fewer days requiring IMV and required fewer antibiotics for respiratory infections. Future work: In patients who fail a SBT, which factors predict an adverse outcome (reintubation, tracheostomy, death) if extubated and weaned using NIV? Trial registration: Current Controlled Trials ISRCTN15635197. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 48. See the NIHR Journals Library website for further project information.

Objectives:. To identify actionable processes of care, quality indicators, or performance measures and their evidence base relevant to patients with persistent or chronic critical illness and their family members including themes relating to patient/family experience. Data Sources:. Two authors independently searched electronic, systemic review, and trial registration databases (inception to November 2016). Study Selection:. We included studies with an ICU length of stay of greater than or equal to 7 days as an inclusion criterion and reported actionable processes of care; quality improvement indicators, measures, or tools; or patient/family experience. We excluded case series/reports of less than 10 patients. Data Extraction:. Paired authors independently extracted data and performed risk of bias assessment. Data Synthesis:. We screened 13,130 references identifying 114 primary studies and 102 relevant reviews. Primary studies reported data on 24,252 participants; median (interquartile range) sample size of 70 (32–182). We identified 42 distinct actionable processes of care, the most commonly investigated related to categories of 1) weaning methods (21 studies; 27 reviews); 2) rehabilitation, mobilization, and physiotherapy (20 studies; 40 reviews); and 3) provision of information, prognosis, and family communication (14 studies; 11 reviews). Processes with limited evidence were generally more patient-centered categories such as communication, promotion of sleep, symptom management, or family support. Of the 21 randomized controlled trials, only two were considered at low risk of bias across all six domains, whereas just two cohort studies and one qualitative study were considered of high quality. Conclusions:. We identified 42 distinct actionable processes of care relevant to patients with persistent or chronic critical illness and their families, with most frequently studied processes relating to weaning, rehabilitation/mobilization, and family communication. Qualitative studies highlighted the need to address psychologic needs and distressing symptoms as well as enabling patient communication. Our findings are informative for clinicians and decision-makers when planning high-quality patient and family-focused care.

Annabel H Nickol1,2, Nicholas Hart1,3, Nicholas S Hopkinson1, Carl-Hugo Hamnegård4, John Moxham5, Anita Simonds1, Michael I Polkey11Respiratory Muscle Laboratory, Royal Brompton Hospital, London, UK; 2Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford, UK; 3The Lane Fox Unit, St Thomas’ Hospital, London, UK; 4Department of Pulmonary Medicine and Clinical Physiology, Sahlgrenska University, Gotenborg, Sweden; 5Respiratory Muscle Laboratory, King’s College London School of Medicine, King’s College Hospital, London, UKBackground: Noninvasive ventilation (NIV) improves gas-exchange and symptoms in selected chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure. We hypothesized NIV reverses respiratory failure by one or all of increased ventilatory response to carbon-dioxide, reduced respiratory muscle fatigue, or improved pulmonary mechanics.Methods: Nineteen stable COPD patients (forced expiratory volume in one second 35% predicted) were studied at baseline (D0), 5–8 days (D5) and 3 months (3M) after starting NIV.Results: Ventilator use was 6.2 (3.7) hours per night at D5 and 3.4 (1.6) at 3M (p = 0.12). Mean (SD) daytime arterial carbon-dioxide tension (PaCO2) was reduced from 7.4 (1.2) kPa to 7.0 (1.1) kPa at D5 and 6.5 (1.1) kPa at 3M (p = 0.001). Total lung capacity decreased from 107 (28) % predicted to 103 (28) at D5 and 103 (27) % predicted at 3M (p = 0.035). At D5 there was an increase in the hypercapnic ventilatory response and some volitional measures of inspiratory and expiratory muscle strength, but not isolated diaphragmatic strength whether assessed by volitional or nonvolitional methods.Conclusion: These findings suggest decreased gas trapping and increased ventilatory sensitivity to CO2 are the principal mechanism underlying improvements in gas-exchange in patients with COPD following NIV. Changes in some volitional but not nonvolitional muscle strength measures may reflect improved patient effort.Keywords: COPD; hypercapnic respiratory failure; NIV; pulmonary mechanics; ventilatory drive