Communication in critical care tracheostomy patients dependent upon cuff inflation: A scoping review.

OBJECTIVES: The aim of this study was to synthesise the evidence concerning communication in critically ill tracheostomy patients dependent on cuff inflation. The aim was to identify the psychological impact on patients awake and alert with tracheostomies but unable to speak; strategies utilised to enable communication and facilitators and barriers for the success of these strategies. REVIEW METHOD USED: This scoping review was conducted using the Joanna Briggs Institute framework and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. DATA SOURCES: CINAHL, Embase, Medline, and Web of Science were searched from 1st January 2000 to 30th September 2023 and supplemented with hand searching of references from included studies. REVIEW METHODS: Studies were eligible if they addressed the psychological impact of voicelessness and/or the structure, process, and outcomes of augmentative and alternative communication (AAC) systems, in addition to facilitators and barriers to effectiveness. The population of interest included critically ill tracheostomy patients dependent on cuff inflation, their families, and healthcare workers. Screening and data extraction were undertaken by two reviewers independently. Data analysis involved descriptive statistics and content analysis. RESULTS: A total of 23 studies met the inclusion criteria: 11 were qualitative, nine were quantitative, and three were mixed-methods studies. Voicelessness elicited negative emotions, predominantly frustration. AAC systems, encompassing unaided and aided (low-tech and high-tech) methods, presented both advantages and drawbacks. High-tech strategies held promise for patients with physical limitations. Patients equally appreciated the support offered through unaided strategies, including eye contact and touch. Facilitating factors included speech therapy involvement and assessment. Patient-related challenges were the most frequent barriers. CONCLUSION: Facilitating meaningful communication for critically ill tracheostomy patients dependent on cuff inflation is of paramount psychological significance. Whilst AAC systems are practicable, they are not without limitations, implying the absence of a universally applicable solution. This underscores the importance of continuous evaluation, reinforced by a multidisciplinary team. REVIEW PROTOCOL REGISTERED: 27 July 2022. REVIEW REGISTRATION: Open Science Framework Registries: https://osf.io/kbrjn/.

Tackling Brain and Muscle Dysfunction in Acute Respiratory Distress Syndrome Survivors: National Heart, Lung, and Blood Institute Workshop Report.

Acute respiratory distress syndrome (ARDS) is associated with long-term impairments in brain and muscle function that significantly impact the quality of life of those who survive the acute illness. The mechanisms underlying these impairments are not yet well understood, and evidence-based interventions to minimize the burden on patients remain unproven. The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health assembled a workshop in April 2023 to review the state of the science regarding ARDS-associated brain and muscle dysfunction, to identify gaps in current knowledge, and to determine priorities for future investigation. The workshop included presentations by scientific leaders across the translational science spectrum and was open to the public as well as the scientific community. This report describes the themes discussed at the workshop as well as recommendations to advance the field toward the goal of improving the health and wellbeing of ARDS survivors.

Rehabilitation outcomes for people with lung cancer (UNITE): protocol for the development of a core outcome set.

INTRODUCTION: With treatment-related improvements in survival, rehabilitation is essential to improve function and health-related quality of life and manage the high symptom burden associated with lung cancer. Despite this, significant heterogeneity exists in the outcomes and instruments used to evaluate lung cancer rehabilitation programme impact. This study aims to develop a core set of clinically relevant lung cancer rehabilitation outcomes for use in clinical practice. METHODS AND ANALYSIS: An international Delphi consensus study involving consumer, healthcare professional and researcher stakeholders to determine which outcomes to include and how to measure these. Stage 1 (preliminary): mixed methods to develop the potential list of outcomes (1) overview of systematic reviews of lung cancer exercise interventions and (2) focus groups and individual interviews with people with lung cancer. Stage 2: outcomes were grouped according to the International Classification of Functioning, Disability and Health domains. Stage 3: to determine priority outcomes for core outcome set (COS) inclusion participants will rate each outcome's importance (one-nine-point Likert scale) over two-three survey rounds. Stage 4: following review by the steering committee, a consensus meeting will be held if agreement on the COS has not been reached.Stage 5: recommendations will be made regarding a single instrument for measuring each COS outcome by reviewing existing resources where consensus has already been reached. Where resources do not exist the quality and feasibility of potential measurement instruments will be appraised, and the Delphi consensus survey and meeting process outlined in stages 3-4 will be repeated.This protocol adheres to the COS-Standardised Protocol statement and will be conducted and reported according to the COS-Standards for Development recommendations and the COS-Standards for Reporting. ETHICS AND DISSEMINATION: Ethics approval (20/9/22, University of Melbourne ID 2022-24839-32231-3). Dissemination in peer-reviewed journals and conference presentations.

From Strict Bedrest to Early Mobilization: A History of Physiotherapy in the Intensive Care Unit.

Critically ill patients are at risk of post-intensive care syndrome, including physical, cognitive, and psychological sequelae. Physiotherapists are rehabilitation experts who focus on restoring strength, physical function, and exercise capacity. Critical care has evolved from a culture of deep sedation and bed rest to one of awakening and early mobility; physiotherapeutic interventions have developed to address patients' rehabilitation needs. Physiotherapists are assuming more prominent roles in clinical and research leadership, with opportunities for wider interdisciplinary collaboration. This paper reviews the evolution of critical care from a rehabilitation perspective, highlights relevant research milestones, and proposes future opportunities for improving survivorship outcomes.

Exercise across the Lung Cancer Care Continuum: An Overview of Systematic Reviews.

BACKGROUND: Growing evidence supports exercise for people with lung cancer. This overview aimed to summarise exercise intervention efficacy and safety across the care continuum. METHODS: Eight databases (including Cochrane and Medline) were searched (inception-February 2022) for systematic reviews of RCTs/quasi-RCTs. Eligibility: population-adults with lung cancer; intervention: exercise (e.g., aerobic, resistance) +/- non-exercise (e.g., nutrition); comparator: usual care/non-exercise; primary outcomes: exercise capacity, physical function, health-related quality of life (HRQoL) and post-operative complications. Duplicate, independent title/abstract and full-text screening, data extraction and quality ratings (AMSTAR-2) were completed. RESULTS: Thirty systematic reviews involving between 157 and 2109 participants (n = 6440 total) were included. Most reviews (n = 28) involved surgical participants. Twenty-five reviews performed meta-analyses. The review quality was commonly rated critically low (n = 22) or low (n = 7). Reviews commonly included combinations of aerobic, resistance and/or respiratory exercise interventions. Pre-operative meta-analyses demonstrated that exercise reduces post-operative complications (n = 4/7) and improves exercise capacity (n = 6/6), whilst HRQoL findings were non-significant (n = 3/3). Post-operative meta-analyses reported significant improvements in exercise capacity (n = 2/3) and muscle strength (n = 1/1) and non-significant HRQoL changes (n = 8/10). Interventions delivered to mixed surgical and non-surgical populations improved exercise capacity (n = 3/4), muscle strength (n = 2/2) and HRQoL (n = 3). Meta-analyses of interventions in non-surgical populations demonstrated inconsistent findings. Adverse event rates were low, however, few reviews reported on safety. CONCLUSIONS: A large body of evidence supports lung cancer exercise interventions to reduce complications and improve exercise capacity in pre- and post-operative populations. Additional higher-quality research is needed, particularly in the non-surgical population, including subgroup analyses of exercise type and setting.

Informing the standardising of care for prolonged stay patients in the intensive care unit: A scoping review of quality improvement tools.

OBJECTIVES: To inform design of quality improvement tools specific to patients with prolonged intensive care unit stay, we determined characteristics (format/content), development, implementation and outcomes of published multi-component quality improvement tools used in the intenisve care unit irrespective of length of stay. RESEARCH METHODOLOGY: Scoping review searching electronic databases, trial registries and grey literature (January 2000 to January 2022). RESULTS: We screened 58,378 citations, identifying 96 studies. All tools were designed for use commencing at intensive care unit admission except three tools implemented at 3, 5 or 14 days. We identified 32 studies of locally developed checklists, 28 goal setting/structured communication templates, 23 care bundles and 9 studies of mixed format tools. Most (43 %) tools were designed for use during rounds, fewer tools were designed for use throughout the ICU day (27 %) or stay (9 %). Most studies (55 %) reported process objectives i.e., improving communication, care standardisation, or rounding efficiency. Most common clinical processes quality improvement tools were used to standardise were sedation (62, 65 %), ventilation and weaning (55, 57 %) and analgesia management (58, 60 %). 44 studies reported the effect of the tool on patient outcomes. Of these, only two identified a negative effect; increased length of stay and increased days with pain and delirium. CONCLUSION: Although we identified numerous quality improvement tools for use in the intensive care unit, few were designed to specifically address actionable processes of care relevant to the unique needs of prolonged stay patients. Tools that address these needs are urgently required. SYSTEMATIC REVIEW REGISTRATION: The review protocol is registered on the Open Science Framework, https://osf.io/, DOI 10.17605/OSF.IO/Z8MRE.

Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.

Importance: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies. Objective: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure. Design, Setting, and Participants: A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. Interventions: Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). Main Outcomes and Measures: The primary outcome was a composite of tracheal intubation or mortality within 30 days. Results: The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings. Trial Registration: isrctn.org Identifier: ISRCTN16912075.

Physical activity of patients with critical illness undergoing rehabilitation in intensive care and on the acute ward: An observational cohort study.

BACKGROUND: There are limited published data on physical activity of survivors of critical illness engaged in rehabilitation in hospital, despite it plausibly influencing outcome. OBJECTIVE: The aims of this study were to measure physical activity of patients with critical illness engaged in rehabilitation in the intensive care unit (ICU) and on the acute ward and report discharge destination, muscle strength, and functional outcomes. METHODS: This was a single-centre, prospective observational study. Adults with critical illness, who received ≥48 h of invasive mechanical ventilation, and who were awake and able to participate in rehabilitation were eligible. To record physical activity, participants wore BodyMedia SenseWear Armbands (BodyMedia Incorporated, USA), during daylight hours, from enrolment until hospital discharge or day 14 of ward stay (whichever occurred first). The primary outcome was time (minutes) spent performing physical activity at an intensity of greater than 1.5 Metabolic Equivalent Tasks. Secondary outcomes included discharge destination, muscle strength, and physical function. RESULTS: We collected 807 days of physical activity data (363 days ICU, 424 days ward) from 59 participants. Mean (standard deviation) duration of daily physical activity increased from the ICU, 17.8 (22.8) minutes, to the ward, 52.8 (51.2) minutes (mean difference [95% confidence interval] = 35 [23.8-46.1] minutes, P < .001). High levels of activity in the ICU were associated with higher levels of activity on the ward (r = .728), n = 48, P < .001. CONCLUSIONS: Patients recovering from critical illness spend less than 5% of the day being physically active throughout hospital admission, even when receiving rehabilitation. Physical activity increased after discharge from intensive care, but had no relationship with discharge destination. Only the absence of ICU-acquired weakness on awakening was associated with discharge directly home from the acute hospital. Future studies could target early identification of ICU-acquired weakness and the preservation of muscle strength to improve discharge outcomes.

Recovery, rehabilitation and follow-up services following critical illness: an updated UK national cross-sectional survey and progress report.

OBJECTIVE: To comprehensively update and survey the current provision of recovery, rehabilitation and follow-up services for adult critical care patients across the UK. DESIGN: Cross-sectional, self-administered, predominantly closed-question, electronic, online survey. SETTING: Institutions providing adult critical care services identified from national databases. PARTICIPANTS: Multiprofessional critical care clinicians delivering services at each site. RESULTS: Responses from 176 UK hospital sites were included (176/242, 72.7%). Inpatient recovery and follow-up services were present at 127/176 (72.2%) sites, adopting multiple formats of delivery and primarily delivered by nurses (n=115/127, 90.6%). Outpatient services ran at 130 sites (73.9%), predominantly as outpatient clinics. Most services (n=108/130, 83.1%) were co-delivered by two or more healthcare professionals, typically nurse/intensive care unit (ICU) physician (n=29/130, 22.3%) or nurse/ICU physician/physiotherapist (n=19/130, 14.6%) teams. Clinical psychology was most frequently lacking from inpatient or outpatient services. Lack of funding was consistently the primary barrier to service provision, with other barriers including logistical and service prioritisation factors indicating that infrastructure and profile for services remain inadequate. Posthospital discharge physical rehabilitation programmes were relatively few (n=31/176, 17.6%), but peer support services were available in nearly half of responding institutions (n=85/176, 48.3%). The effects of the COVID-19 pandemic resulted in either increasing, decreasing or reformatting service provision. Future plans for long-term service transformation focus on expansion of current, and establishment of new, outpatient services. CONCLUSION: Overall, these data demonstrate a proliferation of recovery, follow-up and rehabilitation services for critically ill adults in the past decade across the UK, although service gaps remain suggesting further work is required for guideline implementation. Findings can be used to enhance survivorship for critically ill adults, inform policymakers and commissioners, and provide comparative data and experiential insights for clinicians designing models of care in international healthcare jurisdictions.

Addressing the post-acute sequelae of SARS-CoV-2 infection: a multidisciplinary model of care.

As of July 31, 2021, SARS-CoV-2 had infected almost 200 million people worldwide. The growing burden of survivorship is substantial in terms of the complexity of long-term health effects and the number of people affected. Persistent symptoms have been reported in patients with both mild and severe acute COVID-19, including those admitted to the intensive care unit (ICU). Early reports on the post-acute sequelae of SARS-CoV-2 infection (PASC) indicate that fatigue, dyspnoea, cough, headache, loss of taste or smell, and cognitive or mental health impairments are among the most common symptoms. These complex, multifactorial impairments across the domains of physical, cognitive, and mental health require a coordinated, multidisciplinary approach to management. Decades of research on the multifaceted needs of and models of care for patients with post-intensive care syndrome provide a framework for the development of PASC clinics to address the immediate needs of both hospitalised and non-hospitalised survivors of COVID-19. Such clinics could also provide a platform for rigorous research into the natural history of PASC and the potential benefits of therapeutic interventions.

Relationship Between Skeletal Muscle Area and Density and Clinical Outcome in Adults Receiving Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: To investigate the prevalence of low skeletal muscle index (area normalized for height) and density, their trajectory of change, and to determine associations with clinical outcome in adults with severe respiratory failure requiring venovenous extracorporeal membrane oxygenation. DESIGN: Prospective observational study. PATIENTS: Adults receiving venovenous extracorporeal membrane oxygenation for a minimum of 72 hours and a maximum of 6 months between September 2010 and June 2017, who had a CT scan which included the third lumbar vertebra. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Skeletal muscle index and density was determined using Slice-O-Matic V5.0 (TomoVision, Montreal, QC, Canada). Low skeletal muscle index and density were defined using published criteria. Regression models were used to assess for associations between muscle index and density and clinical outcome. Two-hundred fifteen patients, median (interquartile range) age 46 years (35.0-57.0 yr) were included. Forty-five patients (21.1%) had low skeletal muscle index, and 48 (22.3%) had low skeletal muscle density on commencement of venovenous extracorporeal membrane oxygenation. Low skeletal muscle index was more prevalent in males (28.8% vs 11.6%; χ2 = 9.4; p = 0.002) and was associated with a longer duration of venovenous extracorporeal membrane oxygenation (B = 5.0; 95% CI, 0.2-9.9; p = 0.042). Higher skeletal muscle density was independently associated with ICU survival (odds ratio 1.6 per 10 Hounsfield units; 95% CI, 1.1-2.5; p = 0.025). No relationship was observed between skeletal muscle index nor density and physical function. Adequacy of energy and protein did not influence change in skeletal muscle index or density. CONCLUSIONS: Low skeletal muscle index at the commencement of venovenous extracorporeal membrane oxygenation was associated with a longer duration of venovenous extracorporeal membrane oxygenation, whereas preserved skeletal muscle density was associated with improved survival.

Standardising care in the ICU: a protocol for a scoping review of tools used to improve care delivery.

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.

Airway clearance techniques and use of mucoactive agents for adult critically ill patients with acute respiratory failure: a qualitative study exploring UK physiotherapy practice.

OBJECTIVES: To explore and describe current UK physiotherapy practice relating to airway clearance techniques and mucoactive agents in critically ill adult patients with acute respiratory failure in the intensive care unit. DESIGN: A descriptive, qualitative study using focus group interviews. Focus groups were audio-recorded, independently transcribed, and data analysed thematically. Participants Senior, experienced physiotherapists, clinically active in critical care. RESULTS: Fifteen physiotherapists participated in four interview sessions. Five themes emerged describing airway clearance techniques: 'Repertoire of airway clearance techniques', 'Staffing and skillset', 'Commencing respiratory physiotherapy', 'Technique selection', and 'Determining effectiveness' were themes related to airway clearance techniques. Five themes were also identified in relation to mucoactive agents: 'Use in clinical practice', 'Decision to commence', 'Selection of agent', 'Stopping mucoactive agents', and 'Determining effectiveness'. A summary of key features of standard practice was developed. CONCLUSIONS: Standard UK physiotherapy practice of airway clearance techniques is variable, but patient-centred and targeted to individual need, with adjunctive use of mucoactive agents to enhance and optimise patient management if required. Based on this study, key features of airway clearance techniques have been summarised to help capture standard care, which could be used in future trials involving ACT as part of usual care.

RECOVERY- Respiratory Support: Respiratory Strategies for patients with suspected or proven COVID-19 respiratory failure; Continuous Positive Airway Pressure, High-flow Nasal Oxygen, and standard care: A structured summary of a study protocol for a randomised controlled trial.

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, >=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).