Frail2Fit study protocol: a feasibility and acceptability study of a virtual multimodal intervention delivered by volunteers to improve functional outcomes in older adults with frailty after discharge from hospital.

INTRODUCTION: Physical activity (PA) and replete nutritional status are key to maintaining independence and improving frailty status among frail older adults. In response to the COVID-19 pandemic, healthcare has increasingly turned to virtual modes of delivery and there is interest in the use of trained volunteers to deliver PA and nutrition interventions. We aim to evaluate the feasibility and acceptability of training hospital volunteers to deliver an online intervention, comprising exercise, behaviour change and nutrition support, to older people with frailty after discharge from hospital. METHODS: We will use a quasi-experimental mixed methods approach. Hospital volunteers (n=6) will be trained to deliver an online, 3-month, multimodal intervention to frail (Clinical Frailty Scale ≥5) adults ≥65 years (n=30) after discharge from hospital. Feasibility will be assessed by determining the number of volunteers recruited, trained and retained at the end of the study; the proportion of intervention sessions delivered; participant recruitment, retention and adherence to the intervention. To determine the acceptability of the intervention, interviews will be conducted among a purposive sample of older adults, and volunteers. Secondary outcomes will include physical function, appetite, well-being, quality of life, anxiety and depression, self-efficacy for managing chronic disease and PA. Outcomes will be measured at baseline, 3 months and 6 months. ANALYSIS: Descriptive statistics will be used to describe feasibility and adherence to the intervention. Secondary outcomes at baseline will be compared at 3 and 6 months. Interviews will be transcribed verbatim and analysed using thematic analysis. ETHICS AND DISSEMINATION: Health Research Authority ethical approval was obtained on 30 May 2022 (reference: 22/WA/0155). Results will be disseminated through peer-reviewed journal articles, volunteer organisations, National Health Service communication systems and social media platforms. A toolkit will be developed to facilitate roll out of volunteer training. TRIAL REGISTRATION NUMBER: NCT05384730.

Detailed Analysis of Primary Non-invasive Respiratory Support and Outcomes of Subjects With COVID-19 Acute Hypoxaemic Respiratory Failure.

Background The role of non-invasive (continuous positive airway pressure (CPAP) or Non-invasive ventilation (NIV)) respiratory support (NIRS) as a primary oxygenation strategy for COVID-19 patients with acute severe hypoxic respiratory failure (AHRF), as opposed to invasive mechanical ventilation (invasive-MV), is uncertain. While NIRS may prevent complications related to invasive MV, prolonged NIRS and delays in intubation may lead to adverse outcomes. This study was conducted to assess the role of NIRS in COVID-19 hypoxemic respiratory failure and to explore the variables associated with NRIS failure. Methods This is a single-center, observational study of two distinct waves of severe COVID-19 patients admitted to the ICU. Patients initially managed with non-invasive respiratory support with laboratory-confirmed SARS-CoV-2 in acute hypoxaemic respiratory failure were included. Demographics, comorbidities, admission laboratory variables, and ICU admission scores were extracted from electronic health records. Univariate and multiple logistic regression was used to identify predictive factors for invasive mechanical ventilation. Kaplan-Meier survival curves were used to summarise survival between the ventilatory and time-to-intubation groups. Results There were 291 patients, of which 232 were managed with NIRS as an initial ventilation strategy. There was a high incidence of failure (48.7%). Admission APACHE II score, SOFA score, HACOR score, ROX index, and PaO2/FiO2 were all predictive of NIRS failure. Daily (days 1-4) HACOR scores and ROX index measurements highly predicted NIRS failure. Late NIRS failure (>24 hours) was independently associated with increased mortality (44%). Conclusion NIRS is effective as first-line therapy for COVID-19 patients with AHRF. However, failure, particularly delayed failure, is associated with significant mortality. Early prediction of NIRS failure may prevent adverse outcomes.

Negative Pressure Ventilation for COVID-19 Respiratory Failure: A Phoenix from the Ashes?

Aim: To critically review the clinical question: does negative pressure ventilation (NPV) have a role in the management of COVID-19-associated respiratory failure? Background: NPV was commonly used in the management of respiratory failure until the 1950s when positive pressure devices began to be utilized. Physiological responses to NPV differ from responses to positive pressure ventilation, PPV, in a number of ways that may have clinical advantages in the management of respiratory failure in general, and specifically in the care of COVID-19-associated respiratory failure. Design: Narrative review based on systematic literature research. Data sources: A search on OVID MEDLINE and EMBASE for NPV provided key publications, which were combined with recent relevant literature related to the present COVID-19 pandemic. Results: A total of 83 papers are included in the review and analysis. NPV has been used for >100 years across a range of clinical conditions including polio, adult respiratory distress syndrome, acute respiratory failure in chronic obstructive pulmonary disease patients, a range of neuromuscular disorders, chest wall disease, and post-cardiothoracic and spinal surgery. The potential benefits of NPV, in comparison the treatment of COVID-19 patients, may include improved ventilation, decreased lung damage, improved hemodynamics, ease of proning, and prevention of escalation to intubation. Conclusions: Historic and recent published evidence from animals and man support the use of NPV in acute respiratory failure in general, and strongly suggests that it may be particularly useful in COVID-19-associated respiratory failure. Clinical evaluation of a new lightweight, cost-effective NPV device is justified as it may result in a safe, effective, and economical solution to COVID-19-associated respiratory failure. It could be useful worldwide, but particularly in low and middle-income countries.

A randomised pilot feasibility study of eye movement desensitisation and reprocessing recent traumatic episode protocol, to improve psychological recovery following intensive care admission for COVID-19

Background: Approximately 50% of intensive care survivors experience persistent psychological symptoms. Eye-movement desensitisation and reprocessing (EMDR) is a widely recommended trauma-focussed psychological therapy, which has not been investigated systematically in a cohort of intensive care survivors: We therefore conducted a randomised pilot feasibility study of EMDR, using the Recent Traumatic Episode Protocol (R-TEP), to prevent psychological distress in intensive care survivors. Findings will determine whether it would be possible to conduct a fully-powered clinical effectiveness trial and inform trial design. Method: We aimed to recruit 26 patients who had been admitted to intensive care for over 24 h with COVID-19 infection. Consenting participants were randomised (1:1) to receive either usual care plus remotely delivered EMDR R-TEP or usual care alone (controls). The primary outcome was feasibility. We also report factors related to safety and symptom changes in post-traumatic stress disorder, (PTSD) anxiety and depression. Results: We approached 51 eligible patients, with 26 (51%) providing consent. Intervention adherence (sessions offered/sessions completed) was 83%, and 23/26 participants completed all study procedures. There were no attributable adverse events. Between baseline and 6-month follow-up, mean change in PTSD score was −8 (SD = 10.5) in the intervention group versus +0.75 (SD = 15.2) in controls (p = 0.126). There were no significant changes to anxiety or depression. Conclusion: Remotely delivered EMDR R-TEP met pre-determined feasibility and safety objectives. Whilst we achieved group separation in PTSD symptom change, we have identified a number of protocol refinements that would improve the design of a fully powered, multi-centre randomised controlled trial, consistent with currently recommended rehabilitation clinical pathways. Trial registration: ClinicalTrials.gov: NCT04455360.

Dynamic blood oxygen indices in mechanically ventilated COVID-19 patients with acute hypoxic respiratory failure: A cohort study.

BACKGROUND: Acute hypoxic respiratory failure (AHRF) is a hallmark of severe COVID-19 pneumonia and often requires supplementary oxygen therapy. Critically ill COVID-19 patients may require invasive mechanical ventilation, which carries significant morbidity and mortality. Understanding of the relationship between dynamic changes in blood oxygen indices and clinical variables is lacking. We evaluated the changes in blood oxygen indices-PaO2, PaO2/FiO2 ratio, oxygen content (CaO2) and oxygen extraction ratio (O2ER) in COVID-19 patients through the first 30-days of intensive care unit admission and explored relationships with clinical outcomes. METHODS AND FINDINGS: We performed a retrospective observational cohort study of all adult COVID-19 patients in a single institution requiring invasive mechanical ventilation between March 2020 and March 2021. We collected baseline characteristics, clinical outcomes and blood oxygen indices. 36,383 blood gas data points were analysed from 184 patients over 30-days. Median participant age was 59.5 (IQR 51.0, 67.0), BMI 30.0 (IQR 25.2, 35.5) and the majority were men (62.5%) of white ethnicity (70.1%). Median duration of mechanical ventilation was 15-days (IQR 8, 25). Hospital survival at 30-days was 72.3%. Non-survivors exhibited significantly lower PaO2 throughout intensive care unit admission: day one to day 30 averaged mean difference -0.52 kPa (95% CI: -0.59 to -0.46, p<0.01). Non-survivors exhibited a significantly lower PaO2/FiO2 ratio with an increased separation over time: day one to day 30 averaged mean difference -5.64 (95% CI: -5.85 to -5.43, p<0.01). While all patients had sub-physiological CaO2, non-survivors exhibited significantly higher values. Non-survivors also exhibited significantly lower oxygen extraction ratio with an averaged mean difference of -0.08 (95% CI: -0.09 to -0.07, p<0.01) across day one to day 30. CONCLUSIONS: As a novel cause of acute hypoxic respiratory failure, COVID-19 offers a unique opportunity to study a homogenous cohort of patients with hypoxaemia. In mechanically ventilated adult COVID-19 patients, blood oxygen indices are abnormal with substantial divergence in PaO2/FiO2 ratio and oxygen extraction ratio between survivors and non-survivors. Despite having higher CaO2 values, non-survivors appear to extract less oxygen implying impaired oxygen utilisation. Further exploratory studies are warranted to evaluate and improve oxygen extraction which may help to improve outcomes in severe hypoxaemic mechanically ventilated COVID-19 patients.

Improving physical function of patients following intensive care unit admission (EMPRESS): protocol of a randomised controlled feasibility trial.

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.

SafeFit Trial: virtual clinics to deliver a multimodal intervention to improve psychological and physical well-being in people with cancer. Protocol of a COVID-19 targeted non-randomised phase III trial.

INTRODUCTION: The impact of the COVID-19 pandemic (caused by the SARS-CoV-2 virus) on individuals with cancer has been profound. It has led to increased anxiety, distress and deconditioning due to reduced physical activity. We aim to investigate whether SafeFit, a multimodal intervention of physical activity, nutrition and psychological support delivered virtually by cancer exercise specialists (CES), can improve physical and emotional functionings during the COVID-19 pandemic. METHODS AND ANALYSIS: A phase III non-randomised intervention trial, target recruitment of 1050 adults with suspected or confirmed diagnosis of cancer. All recruited participants will receive the multimodal intervention delivered by CES for 6 months. Sessions will be delivered 1-to-1 using telephone/video conferencing consultations. CES will work with each participant to devise a personalised programme of (1) physical activity, (2) basic dietary advice and (3) psychological support, all underpinned by behaviour change support. PRIMARY OUTCOME: Physical and emotional functioning as measured by the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ-C30). SECONDARY OUTCOMES: overall quality of life measured by EORTC-QLQ-C30 and EQ-5D-5L, health economics, patient activation, self-efficacy to self-manage chronic disease, distress, impact of COVID-19 on emotional functioning, self-reported physical activity, functional capacity and nutrition. Adherence to the intervention will also be measured and a process evaluation conducted. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Health Research Authority (reference number 20/NW/0254). Results of this trial will be disseminated through publication of peer-reviewed articles, presentations at scientific conferences, and to the public and people with cancer in collaboration with our patient and public involvement representatives and partners. TRIAL REGISTRATION NUMBER: NCT04425616.

Vitamin-D levels and intensive care unit outcomes of a cohort of critically ill COVID-19 patients.

OBJECTIVES: The pattern of global COVID-19 has caused many to propose a possible link between susceptibility, severity and vitamin-D levels. Vitamin-D has known immune modulatory effects and deficiency has been linked to increased severity of viral infections. METHODS: We evaluated patients admitted with confirmed SARS-COV-2 to our hospital between March-June 2020. Demographics and outcomes were assessed for those admitted to the intensive care unit (ICU) with normal (>50 nmol/L) and low (<50 nmol/L) vitamin-D. RESULTS: There were 646 SARS-COV-2 PCR positive hospitalisations and 165 (25.5%) had plasma vitamin-D levels. Fifty patients were admitted to ICU. There was no difference in vitamin-D levels of those hospitalised (34, IQR 18.5-66 nmol/L) and those admitted to the ICU (31.5, IQR 21-42 nmol/L). Higher proportion of vitamin-D deficiency (<50 nmol/L) noted in the ICU group (82.0 vs. 65.2%). Among the ICU patients, low vitamin D level (<50 nmol/L) was associated with younger age (57 vs. 67 years, p=0.04) and lower cycle threshold (CT) real time polymerase chain reaction values (RT-PCR) (26.96 vs. 33.6, p=0.02) analogous to higher viral loads. However, there were no significant differences in ICU clinical outcomes (invasive and non-invasive mechanical ventilation, acute kidney injury and mechanical ventilation and hospital days) between patients with low and normal vitamin-D levels. CONCLUSIONS: Despite the association of low vitamin-D levels with low CT values, there is no difference in clinical outcomes in this small cohort of critically ill COVID-19 patients. The complex relationship between vitamin-D levels and COVID-19 infection needs further exploration with large scale randomized controlled trials.

Intensive care physicians' perceptions of the diagnosis & management of patients with acute hypoxic respiratory failure associated with COVID-19: A UK based survey.

Background: Whilst the management of Coronavirus disease-2019 (COVID-19) has evolved in response to the emerging data, treating such patients remains a challenge, and many treatments lack robust clinical evidence. We conducted a survey to evaluate Intensive Care Unit (ICU) management of COVID-19 patients with acute hypoxic respiratory failure and compared the results with data from a similar survey focusing on Acute Respiratory Distress Syndrome (ARDS) that was conducted in 2013. Methods: The questionnaire was refined from a previous survey of ARDS-related clinical practice using an online electronic survey engine (Survey Monkey®) and all UK intensivists were encouraged to participate. The survey was conducted between 16/05/2020 and 17/06/2020. Results: There were 137 responses from 89 UK centres. Non-invasive ventilation was commonly used in the form of CPAP. The primary ventilation strategy was the ARDSnet protocol, with 63% deviating from its PEEP recommendations. Similar to our previous ARDS survey, most allowed permissive targets for hypoxia (94%), hypercapnia (55%) and pH (94%). The routine use of antibiotics was common, and corticosteroids were frequently used, usually in the context of a clinical trial (45%). Late tracheostomy (>7 days) was preferred (92%). Routine follow-up was offered by 66% with few centres providing routine dedicated rehabilitation programmes following discharge. Compared to the ARDS survey, there is an increased use of neuromuscular agents, APRV ventilation and improved provision of rehabilitation services. Conclusions: Similar to our previous ARDS survey, this survey highlights variations in the management strategies used for patients with acute hypoxic respiratory failure due to COVID-19.

Nebulised surfactant for the treatment of severe COVID-19 in adults (COV-Surf): A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: SARS-Cov-2 virus preferentially binds to the Angiotensin Converting Enzyme 2 (ACE2) on alveolar epithelial type II cells, initiating an inflammatory response and tissue damage which may impair surfactant synthesis contributing to alveolar collapse, worsening hypoxia and leading to respiratory failure. The objective of this study is to evaluate the feasibility, safety and efficacy of nebulised surfactant in COVID-19 adult patients requiring mechanical ventilation for respiratory failure. TRIAL DESIGN: This study is a dose-escalating randomized open-label clinical trial of 20 COVID-19 patients. PARTICIPANTS: This study is conducted in two centres: University Hospital Southampton and University College London Hospitals. Eligible participants are aged ≥18, hospitalised with COVID-19 (confirmed by PCR), who require endotracheal intubation and are enrolled within 24 hours of mechanical ventilation. For patients unable to consent, assent is obtained from a personal legal representative (PerLR) or professional legal representative (ProfLR) prior to enrolment. The following are exclusion criteria: imminent expected death within 24 hours; specific contraindications to surfactant administration (e.g. known allergy, pneumothorax, pulmonary hemorrhage); known or suspected pregnancy; stage 4 chronic kidney disease or requiring dialysis (i.e., eGFR < 30); liver failure (Child-Pugh Class C); anticipated transfer to another hospital, which is not a study site, within 72 hours; current or recent (within 1 month) participation in another study that, in the opinion of the investigator, would prevent enrollment for safety reasons; and declined consent or assent. INTERVENTION AND COMPARATOR: Intervention: The study is based on an investigational drug/device combination product. The surfactant product is Bovactant (Alveofact®), a natural animal derived (bovine) lung surfactant formulated as a lyophilized powder in 108 mg vials and reconstituted to 45 mg/mL in buffer supplied in a prefilled syringe. It is isolated by lung lavage and, by weight, is a mixture of: phospholipid (75% phosphatidylcholine, 13% phosphatidylglycerol, 3% phosphatidylethanolamine, 1% phosphatidylinositol and 1% sphingomyelin), 5% cholesterol, 1% lipid-soluble surfactant-associated proteins (SP-B and SP-C), very low levels of free fatty acid, lyso-phosphatidylcholine, water and 0.3% calcium. The Drug Delivery Device is the AeroFact-COVID™ nebulizer, an investigational device based on the Aerogen® Solo vibrating mesh nebulizer. The timing and escalation dosing plans for the surfactant are as follows. Cohort 1: Three patients will receive 10 vials (1080 mg) each of surfactant at dosing times of 0 hours, 8 hours and 24 hours. 2 controls with no placebo intervention. Cohort 2: Three patients will receive 10 vials (1080 mg) of surfactant at dosing times of 0 hours and 8 hours, and 30 vials (3240 mg) at a dosing time of 24 hours. 2 controls with no placebo intervention. Cohort 3: Three patients will receive 10 vials (1080 mg) of surfactant at a dosing time of 0 hours, and 30 vials (3240 mg) at dosing times of 8 hours and 24 hours. 2 controls with no placebo intervention. Cohort 4: Three patients will receive 30 (3240 mg) vials each of surfactant at dosing times of 0 hours, 8 hours and 24 hours. 2 controls. 2 controls with no placebo intervention. The trial steering committee, advised by the data monitoring committee, will review trial progression and dose escalation/maintenance/reduction after each cohort is completed (48-hour primary outcome timepoint reached) based on available feasibility, adverse event, safety and efficacy data. The trial will not be discontinued on the basis of lack of efficacy. The trial may be stopped early on the basis of safety or feasibility concerns. Comparator: No placebo intervention. All participants will receive usual standard of care in accordance with the local policies for mechanically ventilated patients and all other treatments will be left to the discretion of the attending physician. MAIN OUTCOMES: The co-primary outcome is the improvement in oxygenation (PaO2/FiO2 ratio) and pulmonary ventilation (Ventilation Index (VI), where VI = [RR x (PIP - PEEP) × PaCO2]/1000) at 48 hours after study initiation. The secondary outcomes include frequency and severity of adverse events (AEs), Adverse Device Effects (ADEs), Serious Adverse Events (SAEs) and Serious Adverse Device Events (SADEs), change in pulmonary compliance, change in positive end-expiratory pressure (PEEP) requirement of ventilatory support at 24 and 48 hours after study initiation, clinical improvement defined by time to one improvement point on the ordinal scale described in the WHO master protocol (2020) recorded while hospitalised, days of mechanical ventilation, mechanical ventilator free days (VFD) at day 21, length of intensive care unit stay, number of days hospitalised and mortality at day 28. Exploratory end points will include quantification of SARS-CoV-2 viral load from tracheal aspirates using PCR, surfactant dynamics (synthesis and turnover) and function (surface tension reduction) from deep tracheal aspirate samples (DTAS), surfactant phospholipid concentrations in plasma and DTAS, inflammatory markers (cellular and cytokine) in plasma and DTAS, and blood oxidative stress markers. RANDOMISATION: After informed assent, patients fulfilling inclusion criteria will be randomised to 3:2 for the treatment and control arms using an internet-based block randomization service (ALEA tool for clinical trials, FormsVision BV) in combination with electronic data collection. Randomisation will be done by the recruiting centre with a unique subject identifier specific to that centre. BLINDING (MASKING): This is an open-labelled unblinded study. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The total sample size is 20 COVID-19 mechanically ventilated patients (12 intervention; 8 control). TRIAL STATUS: Current protocol version is V2 dated 5th of June 2020. The recruitment is currently ongoing and started on the 14th of October 2020. The anticipated study completion date is November 2021. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04362059 (Registered 24 April 2020), EUDAMED number: CIV-GB-20-06-033328, EudraCT number: 2020-001886-35 (Registered 11 May 2020) FULL PROTOCOL: The full protocol 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).

CovEMERALD: Assessing the feasibility and preliminary effectiveness of remotely delivered Eye Movement Desensitisation and Reprocessing following Covid-19 related critical illness: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Primary Objective: To determine the feasibility of delivering a protocolised, remote, online, Eye Movement Desensitisation and Reprocessing (EMDR) intervention, within 12-weeks of hospital discharge, for adult survivors of Covid-19 related critical illness. Secondary objectives: To investigate whether remotely delivered EMDR can improve psychological outcome following Covid-19 related critical illness, specifically Post-Traumatic Stress Disorder (PTSD), anxiety and depression. TRIAL DESIGN: This is a single centre, randomised controlled cohort feasibility trial. PARTICIPANTS: Participants will be recruited following discharge from the Intensive Care Unit at University Hospital Southampton, United Kingdom. Eligible patients will have received mechanical ventilation for a minimum of 24 hours, tested Covid-19 positive by polymerase chain reaction, will be over the age of 18 years and have the capacity to provide informed consent. Patients will be excluded if they have pre-existing cognitive impairment, pre-existing psychotic diagnosis or are not expected to survive post-hospital discharge. INTERVENTION AND COMPARATOR: Group one: patients in the control arm will receive their standard package of prescribed care, following discharge home from hospital. If they experience any adverse physical or psychological health-conditions, they will access care through the usual available channels. Group two: patients randomly allocated to the intervention arm will receive their standard package of prescribed care, following discharge home from hospital. In addition, they will be referred to the Intensive Psychological Therapies Service in Poole, United Kingdom. They will receive an online appointment within 12-weeks of discharge home from hospital. They will receive a maximum of eight, weekly sessions of EMDR, delivered by a trained psychological therapist, following the Recent Traumatic Episode Protocol (R-TEP). Appendices 1 and 2 of the attached trial protocol contain a detailed description of the R-TEP intervention, written in accordance with the Template for Intervention Description and Replication (TIDieR) checklist and guide. MAIN OUTCOMES: The primary outcome from this trial will be feasibility. Feasibility will be determined by recruitment rates, expressed as a percentage of eligible patients approached, completion of the EMDR intervention, completion of final assessment at 6-months, incidence of attributable adverse events and protocol adherence by the psychological therapists. Secondary, exploratory outcomes will be assessed by comparison between the control and intervention groups at 6-months post-hospital discharge. Psychometric evaluation will consist of the PTSD Checklist-Civilian Version and Hospital Anxiety and Depression Scale. In addition, we will assess health-related quality of life using the EQ5D-5L, physical activity using wrist worn activity monitors and nutritional state using the Council of Nutrition Appetite Questionnaire. RANDOMISATION: Consenting participants will be randomly allocated to intervention or usual care using an internet-based system (ALEATM). Participants will be randomly assigned, on a 1:1 ratio, to receive either standard care (control) or the standard care plus online EMDR R-TEP (Intervention) BLINDING (MASKING): Due to the nature of the intervention, participants cannot be blinded to group allocation. 6-month patient reported outcome measures will be completed using an online, electronic case report form. Group allocation will be masked during data analysis. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This is a feasibility study, the results of which will be used to power a definitive study if appropriate. We anticipate a 25% mortality /loss to follow-up. A total of 26 patients will be recruited to this study, 13 patients in each arm. TRIAL STATUS: CovEMERALD opened to recruitment on 23rd September 2020 with an anticipated recruitment period of 6-months. We are using protocol version number 1.2 (1st June 2020) TRIAL REGISTRATION: CovEMERALD was registered on clinicaltrials.gov NCT04455360 on 2nd July 2020 FULL PROTOCOL: The full protocol 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).

Conscious prone positioning during non-invasive ventilation in COVID-19 patients: experience from a single centre.

Critically ill patients admitted to hospital following SARS-CoV-2 infection often experience hypoxic respiratory failure and a proportion require invasive mechanical ventilation to maintain adequate oxygenation. The combination of prone positioning and non-invasive ventilation in conscious patients may have a role in improving oxygenation. The purpose of this study was to assess the effect of prone positioning in spontaneously ventilating patients receiving non-invasive ventilation admitted to the intensive care.  Clinical data of 81 patients admitted with COVID 19 pneumonia and acute hypoxic respiratory failure were retrieved from electronic medical records and examined. Patients who had received prone positioning in combination with non-invasive ventilation were identified. A total of 20 patients received prone positioning in conjunction with non-invasive ventilation. This resulted in improved oxygenation as measured by a change in PaO 2/FiO 2 (P/F) ratio of 28.7 mmHg while prone, without significant change in heart rate or respiratory rate. Patients on average underwent 5 cycles with a median duration of 3 hours. There were no reported deaths, 7 of the 20 patients (35%) failed non-invasive ventilation and subsequently required intubation and mechanical ventilation. In our cohort of 20 COVID-19 patients with moderate acute hypoxic respiratory failure, prone positioning with non-invasive ventilation resulted in improved oxygenation. Prone positioning with non-invasive ventilation may be considered as an early therapeutic intervention in COVID-19 patients with moderate acute hypoxic respiratory failure.

Oxygen targets in the intensive care unit during mechanical ventilation for acute respiratory distress syndrome: a rapid review.

BACKGROUND: Supplemental oxygen is frequently administered to patients with acute respiratory distress syndrome (ARDS), including ARDS secondary to viral illness such as coronavirus disease 19 (COVID-19). An up-to-date understanding of how best to target this therapy (e.g. arterial partial pressure of oxygen (PaO2) or peripheral oxygen saturation (SpO2) aim) in these patients is urgently required. OBJECTIVES: To address how oxygen therapy should be targeted in adults with ARDS (particularly ARDS secondary to COVID-19 or other respiratory viruses) and requiring mechanical ventilation in an intensive care unit, and the impact oxygen therapy has on mortality, days ventilated, days of catecholamine use, requirement for renal replacement therapy, and quality of life. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, CENTRAL, MEDLINE, and Embase from inception to 15 May 2020 for ongoing or completed randomized controlled trials (RCTs). SELECTION CRITERIA: Two review authors independently assessed all records in accordance with standard Cochrane methodology for study selection. We included RCTs comparing supplemental oxygen administration (i.e. different target PaO2 or SpO2 ranges) in adults with ARDS and receiving mechanical ventilation in an intensive care setting. We excluded studies exploring oxygen administration in patients with different underlying diagnoses or those receiving non-invasive ventilation, high-flow nasal oxygen, or oxygen via facemask. DATA COLLECTION AND ANALYSIS: One review author performed data extraction, which a second review author checked. We assessed risk of bias in included studies using the Cochrane 'Risk of bias' tool. We used the GRADE approach to judge the certainty of the evidence for the following outcomes; mortality at longest follow-up, days ventilated, days of catecholamine use, and requirement for renal replacement therapy. MAIN RESULTS: We identified one completed RCT evaluating oxygen targets in patients with ARDS receiving mechanical ventilation in an intensive care setting. The study randomized 205 mechanically ventilated patients with ARDS to either conservative (PaO2 55 to 70 mmHg, or SpO2 88% to 92%) or liberal (PaO2 90 to 105 mmHg, or SpO2 ≥ 96%) oxygen therapy for seven days. Overall risk of bias was high (due to lack of blinding, small numbers of participants, and the trial stopping prematurely), and we assessed the certainty of the evidence as very low. The available data suggested that mortality at 90 days may be higher in those participants receiving a lower oxygen target (odds ratio (OR) 1.83, 95% confidence interval (CI) 1.03 to 3.27). There was no evidence of a difference between the lower and higher target groups in mean number of days ventilated (14.0, 95% CI 10.0 to 18.0 versus 14.5, 95% CI 11.8 to 17.1); number of days of catecholamine use (8.0, 95% CI 5.5 to 10.5 versus 7.2, 95% CI 5.9 to 8.4); or participants receiving renal replacement therapy (13.7%, 95% CI 5.8% to 21.6% versus 12.0%, 95% CI 5.0% to 19.1%). Quality of life was not reported. AUTHORS' CONCLUSIONS: We are very uncertain as to whether a higher or lower oxygen target is more beneficial in patients with ARDS and receiving mechanical ventilation in an intensive care setting. We identified only one RCT with a total of 205 participants exploring this question, and rated the risk of bias as high and the certainty of the findings as very low. Further well-conducted studies are urgently needed to increase the certainty of the findings reported here. This review should be updated when more evidence is available.