Imperial College London

ProfessorStephenBrett

Faculty of MedicineDepartment of Surgery & Cancer

Professor of Critical Care
 
 
 
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Contact

 

+44 (0)20 3313 4521stephen.brett Website

 
 
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Location

 

Hammersmith House 570Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

248 results found

Huq F, manners E, O'Callaghan D, Thakuria L, Weaver C, Waheed U, Stümpfle R, Brett SJ, Patel P, Soni Set al., 2022, Patient outcomes following transfer between intensive care units during the COVID-19 pandemic, Anaesthesia, ISSN: 0003-2409

Journal article

Grailey K, Lound A, Brett S, 2021, Lived experiences of healthcare workers on the frontline during the COVID-19 pandemic – a qualitative interview study., BMJ Open, Vol: 11, Pages: 1-13, ISSN: 2044-6055

Objectives: This study aimed to investigate the presence of perceived stressors, psychological safety and teamwork in healthcare professionals. As the timeframe for this study spanned the first wave of the COVID-19 pandemic, data were captured demonstrating the impact of the pandemic on these factors. Design: Qualitative Interview Study Setting: All staff working within the Emergency and Critical Care Departments of one National Health Service Trust in London, United Kingdom. Participants: Forty-nine participants were recruited using a purposive sampling technique and interviewed when the first wave of the COVID-19 pandemic had subsided. Main Outcome Measures: Evaluation of changes in perceived stressors, psychological safety and teamwork in individuals working during the COVID-19 pandemic. Results: The thematic analysis relating to a participant’s lived experiences whilst working during COVID-19 led to the construction of 5 key themes, including ‘Psychological effects’ and ‘Changes in team dynamics’. Several psychological effects were described, including the presence of psychological distress and insights into the aetiology of moral injury. There was marked heterogeneity in participants response to COVID-19, particularly with respect to changes in team dynamics and the perception of a psychologically safe environment. Descriptions of improved team cohesiveness and camaraderie contrasted with stories of new barriers, notably due to the high workload and the impact of personal protective equipment. Building on these themes, a map of key changes arising due to the pandemic was developed, highlighting potential opportunities to provide targeted support. Conclusions: Working on the frontline of a pandemic can have significant implications for healthcare workers, putting them at risk of psychological distress and moral injury, as well as affecting team dynamics. There is striking heterogeneity in the manifestation of these challenges.

Journal article

Schutzer-Weissmann J, Wojcikiewicz T, Karmali A, Lukosiute A, Sun R, Ahmed A, Purkayastha S, Brett S, Cousins Jet al., 2021, Apnoeic oxygenation in morbid obesity: a randomised controlled trial comparing facemask and high-flow nasal oxygen delivery, British Journal of Anaesthesia, ISSN: 0007-0912

BackgroundObesity is a risk factor for airway-related incidents during anaesthesia. High flow nasal oxygen has been advocated to improve safety in high-risk groups but its effectiveness in the obese population is uncertain. This study compared the effect of high flow nasal oxygen and low flow facemask oxygen delivery on duration of apnoea in morbidly-obese patients.MethodsPatients undergoing bariatric surgery were randomly allocated to receive either high flow nasal (70 L min-1) or facemask (15 L min-1) oxygen. Following induction of anaesthesia, morbidly-obese patients were apnoeic for 18 minutes or until oxygen saturation dropped to 92%.ResultsEighty patients were studied (41 high flow nasal oxygen, 39 facemask). Median apnoea duration was 18 minutes in both the high flow nasal oxygen (IQR 18-18 minutes) and the facemask (IQR 4.1-18 minutes) groups. Five patients in the high flow nasal oxygen group and 14 patients in the facemask group desaturated to 92% within 18 minutes. The risk of desaturation was lower in the high flow nasal oxygen group (Hazard Ratio 0.27, 95% CI 0.11-0.65, p=0.007). ConclusionsIn experienced hands, apnoeic oxygenation is possible in the morbidly-obese and was tolerated for 18 minutes by the majority of patients, whether oxygen delivery was high flow nasal or low flow facemask. High flow nasal oxygen reduced desaturation risk compared to facemask oxygen. Desaturation risk is a more clinically relevant outcome than duration of apnoea. Individual physiological factors are likely to be the primary determinant of risk rather than method of oxygen delivery.

Journal article

Grailey K, Leon-Villapalos C, Murray E, Brett Set al., 2021, The psychological impact of the workplace environment in critical care a qualitative exploration, Human Factors in Healthcare, Vol: 1, Pages: 1-6, ISSN: 2772-5014

The workplace environment can have a significant impact on an employee’s psychological wellbeing. This has been demonstrated using the Job Demand Control Model, which posits that high job demands and low decision latitude lead to increased job strain.Participants were recruited from three Critical Care Units within one NHS Trust in London. Each participant underwent a qualitative interview exploring attitudes to the workplace environment and its subsequent impact. Data were analysed using a thematic analysis approach. Thirty participants representing the multidisciplinary team and all levels of seniority were recruited according to a purposeful sampling technique. Our analysis demonstrated a measurable incidence of negative psychological consequences resulting from several key areas within the critical care environment, including isolation in single rooms and visibility of senior support. Applying the Job Demand Control model, we were able to identify areas of high job demand and low decision latitude. The critical care environment is highly dynamic and job demands are likely to be unmodifiable. The framework developed in this study highlights areas that can be adapted to improve decision latitude, consequently minimising negative consequences. Leaders wishing to improve the psychological wellbeing of their staff can use our framework to identify areas where individual control can be enhanced. This should lead to increased decision latitude, thereby reducing the psychological strain created by the workplace environment. In addition, a reduction in job strain and improved employee wellbeing may create more commitment to the organisation, improving productivity and enhancing career longevity.

Journal article

Reader T, Dayal R, Brett S, 2021, At the end: a vignette-based investigation of strategies for managing end-of-life decisions in the Intensive Care Unit, Journal of the Intensive Care Society, Vol: 22, Pages: 305-311, ISSN: 1751-1437

Background. Decision-making on End-of-life (EOL) is an inevitable, yet highly complex, aspect of intensive care decision-making. EOL decisions can be challenging both in terms of clinical judgement and social interaction with families, and these two process often become intertwined. This is especially apparent at times when clinicians are required to seek the views of surrogate decision makers (i.e., family members) when considering palliative care. Methods. Using a vignette-based interview methodology, we explored how interactions with family members influence EOL decisions by ICU clinicians (n=24), and identified strategies for reaching consensus with families during this highly emotional phase of ICU care. Results. We found that the enactment of EOL decisions were reported as being affected by a form of loss aversion, whereby concerns over the consequences of not reaching a consensus with families weighed heavily in the minds of clinicians. Fear of conflict with families tended to arise from anticipated unrealistic family expectations of care, family normalization of patient incapacity, and belief systems that prohibit end-of-life decision-making. Conclusions. To support decision makers in reaching consensus, various strategies for effective, coherent, and targeted communication (e.g., patient deterioration and limits of clinical treatment) were suggested as ways to effectively consult with families on EOL decision-making.

Journal article

Shah A, MacCallum N, Harris S, Brealey D, Palmer E, Hetherington J, Shi S, Perez-Suarez D, Ercole A, Watkinson P, Jones A, Ashworth S, Beale R, Brett S, Singer Met al., 2021, Descriptors of sepsis using the Sepsis-3 criteria: a cohort study in critical care units within the UK NIHR Critical Care Health Informatics Collaborative, Critical Care Medicine, Vol: 49, Pages: 1883-1894, ISSN: 0090-3493

Objective: To describe the epidemiology of sepsis in critical care by applying the Sepsis-3 criteria to electronic health records. Design: Retrospective cohort study using electronic health records. Setting: Ten intensive care units (ICU) from four United Kingdom National Health Service hospital trusts contributing to the National Institute for Health Research Critical Care Health Informatics Collaborative (CC-HIC).Patients: 28,456 critical care admissions (14,332 emergency medical, 4,585 emergency surgical, and 9,539 elective surgical)Measurements and Main Results: 29,343 episodes of clinical deterioration were identified with a rise in Sequential Organ Failure Assessment (SOFA) score of at least 2 points, of which 14,869 (50.7%) were associated with antibiotic escalation and thereby met the Sepsis-3 criteria for sepsis. 4,100 episodes of sepsis (27.6%) were associated with vasopressor use and lactate > 2.0 mmol/l, and therefore met the Sepsis-3 criteria for septic shock. ICU mortality by source of sepsis was highest for ICU-acquired sepsis (23.7%, 95% CI 21.9%, 25.6%), followed by hospital-acquired sepsis (18.6%, 95% CI 17.5%, 19.9%), and community-acquired sepsis (12.9%, 95% CI 12.1%, 13.6%) (p for comparison <0.0001).Conclusions: We successfully operationalized the Sepsis-3 criteria to an electronic health record dataset to describe the characteristics of critical care patients with sepsis. This may facilitate sepsis research using electronic health record data at scale without relying on human coding.

Journal article

Warner B, Harry A, Brett S, Wells M, Antcliffe Det al., 2021, The end is just the beginning: involvement of bereaved next of kin in qualitative research, BMJ Supportive & Palliative Care, ISSN: 2045-4368

Journal article

Stacey M, Hill N, Brett S, Fitchett G, Woods Det al., 2021, What do environment-related illnesses tell us about the character of military medicine and future clinical requirements?, BMJ Military Health, ISSN: 2633-3767

Extreme environments present medical and occupational challenges that extend beyond generic resuscitation, to formulating bespoke diagnoses and prognoses and embarking on management pathways rarely encountered in civilian practice. Pathophysiological complexity and clinical uncertainty call for military physicians of all kinds to balance intuition with pragmatism, adapting according to the predominant patterns of care required. In an era of smaller operational footprints and less concentrated clinical experience, proposals aimed at improving the systematic care of Service Personnel incapacitated at environmental extremes must not be lost to corporate memory. These general issues are explored in the particular context of thermal stress and metabolic disruption. Specific focus is given to the accounts of military physicians who served on large-scale deployments into the heat of Iraq and Kuwait (Operation TELIC) and Oman (Exercise SAIF SAREEA). Generalisable insights into the enduring character of military medicine and future clinical requirements result.

Journal article

Look N, Voss S, Blennow Nordström E, Brett S, Jenkinson E, Shaw P, White P, Benger Jet al., 2021, Neurocognitive function following out-of-hospital cardiac arrest: a systematic review, Resuscitation, ISSN: 0300-9572

ObjectivesThe primary aim of this review was to investigate neurocognitive outcomes following out-of-hospital cardiac arrest (OHCA). Specifically, the focus was on identifying the different neurocognitive domains that are assessed, the measures used, and the level of, and criteria for, impairment.Design and review methodsA systematic review of the literature from 2006 to 2021 was completed using Medline, Cinahl and Psychinfo. Criteria for inclusion were studies with participants over the age of 18, OHCA and at least one neurocognitive function measure. Qualitative and case studies were excluded. Reviewers assessed criteria and risk of bias using a modified version of Downs and Black.ResultsForty-three studies were identified. Most studies had a low risk of bias (n = 31) or moderate risk of bias (n = 11) and one had a high risk; however, only six reported effect sizes or power analyses. Multiple measures of neurocognitive outcomes were used (>50) and level of impairment criteria varied considerably. Memory impairments were frequently found and were also more likely to be impaired followed by executive function and processing speed.DiscussionThis review highlights the heterogeneity of measures and approaches used to assess neurocognitive outcomes following OHCA as well as the need to improve risk of bias concerning generalizability. Improved understanding of the approaches used for assessment and the subsequent findings will facilitate a standardized evaluation of neurocognitive outcomes following OHCA.

Journal article

Stokes E, Lazaroo M, Clout M, Brett S, Black S, Kirby K, Nolan J, Reeves B, Robinson M, Rogers C, Scott L, Smartt H, South A, Taylor J, Thomas M, Voss S, Benger J, Wordsworth Set al., 2021, Cost-effectiveness of the i-gel supraglottic airway device compared to tracheal intubation during out-of-hospital cardiac arrest: findings from the AIRWAYS-2 randomised controlled trial, Resuscitation, Vol: 167, Pages: 1-9, ISSN: 0300-9572

Aim:Optimal airway management during out-of-hospital cardiac arrest (OHCA) is uncertain. Complications from tracheal intubation (TI) may be avoided with supraglottic airway (SGA) devices. The AIRWAYS-2 cluster randomised controlled trial (ISRCTN08256118) compared the i-gel SGA with TI as the initial advanced airway management (AAM) strategy by paramedics treating adults with non-traumatic OHCA. This paper reports the trial cost-effectiveness analysis.Methods:A within-trial cost-effectiveness analysis of the i-gel compared with TI was conducted, with a 6-month time horizon, from the perspective of the UK National Health Service (NHS) and personal social services. The primary outcome measure was quality-adjusted life years (QALYs), estimated using the EQ-5D-5L questionnaire. Multilevel linear regression modelling was used to account for clustering by paramedic when combining costs and outcomes.Results:9,296 eligible patients were attended by 1,382 trial paramedics and enrolled in the AIRWAYS-2 trial (4410 TI, 4886 i-gel). Mean QALYs to 6 months were 0.03 in both groups (i-gel minus TI difference -0.0015, 95% CI –0.0059 to 0.0028). Total costs per participant up to 6 months post-OHCA were £3,570 and £3,413 in the i-gel and TI groups respectively (mean difference £157, 95% CI –£270 to £583). Based on mean difference point estimates, TI was more effective and less costly than i-gel; however differences were small and there was great uncertainty around these results.Conclusion:The small differences between groups in QALYs and costs shows no difference in the cost-effectiveness of the i-gel and TI when used as the initial AAM strategy in adults with non-traumatic OHCA.

Journal article

Glampson B, Brittain J, Kaura A, Mulla A, Mercuri L, Brett S, Aylin P, tessa S, goodman I, Redhead J, kavitha S, Mayer Eet al., 2021, North West London Covid-19 Vaccination Programme: Real-world evidence for Vaccine uptake and effectiveness: Retrospective Cohort Study, JMIR Public Health and Surveillance, Vol: 7, Pages: 1-17, ISSN: 2369-2960

Background:On March 11, 2020 the World Health Organisation declared the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causing Coronavirus Disease 2019 (COVID-19) syndrome, as a pandemic. The UK mass vaccination programme commenced on December 08, 2020 vaccinating groups of the population deemed to be most vulnerable to severe COVID-19 infection.Objective:To assess the early vaccine administration coverage and outcome data across an integrated care system in North West London (NWL), leveraging a unique population-level care dataset. Vaccine effectiveness of a single dose of the Oxford/Astrazeneca and Pfizer/BioNtech vaccines were compared.Methods:A retrospective cohort study identified 2,183,939 individuals eligible for COVID-19 vaccination between December 08, 2020 and February 24, 2021 within a primary, secondary and community care integrated care dataset. These data were used to assess vaccination hesitancy across ethnicity, gender and socio-economic deprivation measures (Pearson Product-Moment Correlations); investigated COVID-19 transmission related to vaccination hubs; and assessed the early effectiveness of COVID-19 vaccination (after a single dose) using time to event analyses with multivariable Cox regression analysis to investigate if vaccination independently predicted positive SARS-CoV-2 in those vaccinated compared to those unvaccinated.Results: In the study 5.88% (24,332/413,919) of individuals declined and did not receive a vaccination. Black or Black British individuals had the highest rate of declining a vaccine at 16.14% (4,337/26,870). There was a strong negative association between socio-economic deprivation and rate of declining vaccination (r=-0.94, P=.002) with 13.5% (1980/14571) of individuals declining vaccination in the most deprived areas compared to 0.98% (869/9609) in the least. In the first six days after vaccination 344 of 389587 individuals tested positive for SARS-CoV-2 (0.09%). The rate increased to 0.13% (525/389,243)

Journal article

Billot L, Lipman J, Brett SJ, De Waele JJ, Cotta MO, Davis JS, Finfer S, Hammond N, Knowles S, McGuinness S, Myburgh J, Paterson DL, Peake S, Rajbhandari D, Rhodes A, Roberts JA, Roger C, Shirwadkar C, Starr T, Taylor C, Dulhunty JMet al., 2021, Statistical analysis plan for the BLING III study: a phase 3 multicentre randomised controlled trial of continuous versus intermittent beta-lactam antibiotic infusion in critically ill patients with sepsis, Critical Care and Resuscitation, Vol: 23, Pages: 273-284, ISSN: 1441-2772

BACKGROUND: The β-Lactam Infusion Group (BLING) III study is a prospective, multicentre, open, phase 3 randomised controlled trial comparing continuous infusion with intermittent infusion of β-lactam antibiotics in 7000 critically ill patients with sepsis.OBJECTIVE: To describe a statistical analysis plan for the BLING III study.METHODS: The statistical analysis plan was designed by the trial statistician and chief investigators and approved by the BLING III management committee before the completion of data collection. Statistical analyses for primary, secondary and tertiary outcomes and planned subgroup analyses are described in detail. Interim analysis by the Data Safety and Monitoring Committee (DSMC) has been conducted in accordance with a pre-specified DSMC charter.RESULTS AND CONCLUSIONS: The statistical analysis plan for the BLING III study is published before completion of data collection and unblinding to minimise analysis bias and facilitate public access and transparent analysis and reporting of study findings.TRIAL REGISTRATION: ClinicalTrials.gov Registry NCT03212990.

Journal article

Grailey K, Murray E, Reader T, Brett Set al., 2021, The presence and potential impact of psychological safety in the healthcare setting: An evidence synthesis, BMC Health Services Research, Vol: 21, Pages: 1-15, ISSN: 1472-6963

IntroductionPsychological safety is the shared belief that the team is safe for interpersonal risk taking. Its presence improves innovation and error prevention. This evidence synthesis had 3 objectives: explore the current literature regarding psychological safety, identify methods used in its assessment and investigate for evidence of consequences of a psychologically safe environmentMethodsWe searched multiple trial registries through December 2018. All studies addressing psychological safety within healthcare workers were included and reviewed for methodological limitations. A thematic analysis approach explored the presence of psychological safety. Content analysis was utilised to evaluate potential consequences.ResultsWe included 62 papers from 19 countries. The thematic analysis demonstrated high and low levels of psychological safety both at the individual level in study participants and across the studies themselves. There was heterogeneity in responses across all studies, limiting generalisable conclusions about the overall presence of psychological safety. A wide range of methods were used. Twenty-five used qualitative methodology, predominantly semi-structured interviews. Thirty quantitative or mixed method studies used surveys. Ten studies inferred that low psychological safety negatively impacted patient safety. Nine demonstrated a significant relationship between psychological safety and team outcomes. The thematic analysis allowed the development of concepts beyond the content of the original studies. This analytical process provided a wealth of information regarding facilitators and barriers to psychological safety and the development of a model demonstrating the influence of situational context.Discussion This evidence synthesis highlights that whilst there is a positive and demonstrable presence of psychological safety within healthcare workers worldwide, there is room for improvement. The variability in methods used demonstrates scope to harmonis

Journal article

Grailey K, Leon-Villapolos C, Murray E, Brett Set al., 2021, Exploring the factors which promote or diminish a psychologically safe environment: a qualitative interview study with critical care staff., BMJ Open, Vol: 11, Pages: 1-8, ISSN: 2044-6055

ObjectivesThis study aimed to quantify the presence of psychological safety (defined as an environment “safe for interpersonal risk taking”) in critical care staff, exploring the ways in which this manifestedDesignQualitative interview study incorporating a short quantitative survey. SettingThree Intensive Care Units within one NHS Trust in London ParticipantsThirty participants were recruited from all levels of seniority and roles within the multidisciplinary team. A purposive sampling technique was used, with recruitment ceasing at the point of thematic saturation. InterventionsSemi-structured interviews explored attitudes towards psychological safety and contained a quantitative assessment measuring the climate of psychological safety present. ResultsTwenty-eight participants agreed that it was easy to ask for help, with 20 agreeing it is safe to take a risk on the team, demonstrating a strong perception of psychological safety in this group. Our thematic analysis highlighted areas where the context influenced an individual’s psychological safety including personality, culture & leadership. Possible negative consequences of psychological safety included distraction and fatigue for the team leader. We demonstrated that speaking up can be influenced by motivations other than patient safety – such as undermining or self-promotion. ConclusionsOur data demonstrate reassuring levels of psychological safety within the participants studied. This allowed us to explore in depth the participant experience of working within a psychologically safe environment. We add to the current literature by uniquely demonstrating there can be negative consequences to a psychologically safe environment in the healthcare setting. We expand on the influence of context on psychological safety by developing a model – allowing leaders to identify which elements of context can be modified in order to promote speaking up. Team leaders can use this data to help f

Journal article

Goodwin L, Samuel K, Schofield B, Voss S, Brett S, Couper K, Gould D, Harrison D, Lall R, Nolan J, Perkins G, Soar J, Thomas M, Benger Jet al., 2021, Airway management during in-hospital cardiac arrest (IHCA) in adults: UK national survey and interview study with anaesthetic and intensive care trainees, Journal of the Intensive Care Society, Vol: 22, Pages: 192-197, ISSN: 1751-1437

Background: The optimal airway management strategy for in-hospital cardiac arrest (IHCA) is unknown.Methods: An online survey and telephone interviews with anaesthetic and intensive care trainee doctors identified by the United Kingdom (UK) Research and Audit Federation of Trainees. Questions explored IHCA frequency, grade and specialty of those attending, proportion of patients receiving advanced airway management, airway strategies immediately available, and views on a randomised trial of airway management strategies during IHCA.Results: Completed surveys were received from 128 hospital sites (76% response rate). Adult IHCAs were attended by anaesthesia staff at 40 sites (31%), intensive care staff at 37 sites (29%), and a combination of specialties at 51 sites (40%). The majority (123/128, 96%) of respondents reported immediate access to both tracheal intubation (TI) and supraglottic airways (SGAs). A bag-mask technique was used ‘very frequently’ or ‘frequently’ during IHCA by 111/128 (87%) of respondents, followed by SGAs (101/128, 79%) and TI (69/128, 54%). The majority (60/100, 60%) of respondents estimated that ≤30% of IHCA patients undergo TI, while 34 (34%) estimated this to be between 31-70%. Most respondents (102/128, 80%) would be ‘likely’ or ‘very likely’ to recruit future patients to a trial of alternative airway management strategies during IHCA. Interview data identified several barriers and facilitators to conducting research on airway management in IHCA.Conclusions: There is variation in airway management strategies for adult IHCA across the UK. Most respondents would be willing to take part in a randomised trial of airway management during IHCA.

Journal article

COVID-19 Host Genetics Initiative, 2021, Mapping the human genetic architecture of COVID-19, Nature, Vol: 600, Pages: 472-477, ISSN: 0028-0836

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3-7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

Journal article

Glampson B, Brittain J, Kaura A, Mulla A, Mercuri L, Brett SJ, Aylin P, Sandall T, Goodman I, Redhead J, Saravanakumar K, Mayer EKet al., 2021, Assessing COVID-19 vaccine uptake and effectiveness through the north west London vaccination program: retrospective cohort study, Publisher: JMIR Publications

Background:Real world data supporting the effectiveness of the COVID-19 vaccination strategy in the UK population is needed to guide health policy. This real-word data-driven evidence study of the UK COVID-19 Vaccination Programme in the Northwest London (NWL) population used a unique dataset established as part of the Gold Command Covid-19 response in NWL (iCARE https://imperialbrc.nihr.ac.uk/facilities/icare/), which included the pre-established Whole System Integrated Care (WSIC) data collated for the purposes of population health in the sector.Objective:To assess the early vaccine administration coverage and vaccine effectiveness and outcome data across an integrated care system of eight CCGs leveraging a unique population-level care datasetMethods:Design - Retrospective cohort study. Setting - Individuals eligible for COVID 19 vaccination in North West London based on linked primary and secondary care data. Participants - 2,183,939 individuals eligible for COVID 19 vaccinationResults:During the NWL vaccine programme study time period 5.88% of individuals declined and did not receive a vaccination. Black or black British individuals had the highest rate of declining a vaccine at 16.14% (4,337). There was a strong negative association between deprivation and rate of declining vaccination (r=-0.94, p<0.01) with 13.5% of individuals declining vaccination in the most deprived postcodes compared to 0.98% in the least deprived postcodes. In the first six days after vaccination 344 of 389587 individuals tested positive for COVID-19 (0.09%). The rate increased to 0.13% (525/389,243) between days 7 and 13, before then gradually falling week on week. At 28 days post vaccination there was a 74% (HR 0.26 (0.19-0.35)) and 78% (HR 0.22 (0.18-0.27)) reduction in risk of testing positive for COVID -19 for individuals that received the Oxford/Astrazeneca and Pfizer/BioNTech vaccines respectively, when compared with unvaccinated individuals. After vaccination very low rates of

Working paper

Pandolfo A, Horne R, Jani Y, Reader T, Bidad N, Brealey D, Enne V, Livermore D, Gant V, Brett Set al., 2021, Intensivists’ beliefs about rapid multiplex molecular diagnostic testing and its potential role in improving prescribing decisions and antimicrobial stewardship: a qualitative study, Antimicrobial Resistance and Infection Control, Vol: 10, Pages: 1-8, ISSN: 2047-2994

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

Journal article

Pandolfo A, Horne R, Yogini J, Reader T, Bidad N, Brealey D, Enne V, Livermore D, Gant V, Brett Set al., 2021, Understanding decisions about antibiotic prescribing in ICU: an application of the Necessity Concerns Framework, BMJ Quality and Safety, ISSN: 2044-5415

Background: Antibiotics are extensively prescribed in intensive care units (ICUs), yet little is known about how antibiotic-related decisions are made in this setting. We explored how beliefs, perceptions and contextual factors influenced ICU clinicians’ antibiotic prescribing.Methods: We conducted 4 focus groups and 34 semistructured interviews with clinicians involved in antibiotic prescribing in four English ICUs. Focus groups explored factors influencing prescribing, whereas interviews examined decision-making processes using two clinical vignettes. Data were analysed using thematic analysis, applying the Necessity Concerns Framework.Results: Clinicians’ antibiotic decisions were influenced by their judgement of the necessity for prescribing/not prescribing, relative to their concerns about potential adverse consequences. Antibiotic necessity perceptions were strongly influenced by beliefs that antibiotics would protect patients from deterioration and themselves from the ethical and legal consequences of undertreatment. Clinicians also reported concerns about prescribing antibiotics. These generally centred on antimicrobial resistance; however, protecting the individual patient was prioritised over these societal concerns. Few participants identified antibiotic toxicity concerns as a key influencer. Clinical uncertainty often complicated balancing antibiotic necessity against concerns. Decisions to start or continue antibiotics often represented ‘erring on the side of caution’ as a protective response in uncertainty. This approach was reinforced by previous experiences of negative consequences (‘being burnt’) which motivated prescribing ‘just in case’ of an infection. Prescribing decisions were also context-dependent, exemplified by a lower perceived threshold to prescribe antibiotics out-of-hours, input from external team members and local prescribing norms.Conclusion: Efforts to improve antibiotic stewardship sho

Journal article

Coughlan C, Ranisz W, Leon-Villapolas C, Newey V, Boynton C, Corner E, Sturmey G, Wiltshire M, Brett Set al., 2021, Rehabilitation after critical illness-don't overlook technological and social factors., BMJ, Vol: 373, Pages: n1403-n1403, ISSN: 1759-2151

Journal article

Stephens J, Wong J, Broomhead R, Stumpfle R, Waheed U, Patel P, Brett S, Soni Set al., 2021, Raised serum amylase in patients with COVID-19 may not be associated with pancreatitis, British Journal of Surgery, Vol: 108, Pages: 152-153, ISSN: 0007-1323

Journal article

Lannou EL, Post B, Haar S, Brett SJ, Kadirvelu B, Faisal AAet al., 2021, Clustering of patient comorbidities within electronic medical records enables high-precision COVID-19 mortality prediction

<jats:title>Abstract</jats:title><jats:p>We present an explainable AI framework to predict mortality after a positive COVID-19 diagnosis based solely on data routinely collected in electronic healthcare records (EHRs) obtained prior to diagnosis. We grounded our analysis on the ½ Million people UK Biobank and linked NHS COVID-19 records. We developed a method to capture the complexities and large variety of clinical codes present in EHRs, and we show that these have a larger impact on risk than all other patient data but age. We use a form of clustering for natural language processing of the clinical codes, specifically, topic modelling by Latent Dirichlet Allocation (LDA), to generate a succinct digital fingerprint of a patient’s full secondary care clinical history, i.e. their comorbidities and past interventions. These digital comorbidity fingerprints offer immediately interpretable clinical descriptions that are meaningful, e.g. grouping cardiovascular disorders with common risk factors but also novel groupings that are not obvious. The comorbidity fingerprints differ in both their breadth and depth from existing observational disease associations in the COVID-19 literature. Taking this data-driven approach allows us to avoid human-induction bias and confirmation bias during selection of what are important potential predictors of COVID-19 mortality. Together with age, these digital fingerprints are the single most important factor in our predictor. This holds the potential for improving individual risk profiling for clinical decisions and the identification of groups for public health interventions such as vaccine programmes. Combining our digital precondition fingerprints with demographic characteristics allow us to match or exceed the performance of existing state-of-the-art COVID-19 mortality predictors (EHCF) which have been developed through expert consensus. Our precondition fingerprinting and entire mortality prediction anal

Journal article

Rousseau A-F, Prescott HC, Brett SJ, Weiss B, Azoulay E, Creteur J, Latronico N, Hough CL, Weber-Carstens S, Vincent J-L, Preiser J-Cet al., 2021, Long-term outcomes after critical illness: recent insights, Critical Care (UK), Vol: 25, ISSN: 1364-8535

Intensive care survivors often experience post-intensive care sequelae, which are frequently gathered together under the term “post-intensive care syndrome” (PICS). The consequences of PICS on quality of life, health-related costs and hospital readmissions are real public health problems. In the present Viewpoint, we summarize current knowledge and gaps in our understanding of PICS and approaches to management.

Journal article

Pairo-Castineira E, Clohisey S, Klaric L, Bretherick AD, Rawlik K, Pasko D, Walker S, Parkinson N, Fourman MH, Russell CD, Furniss J, Richmond A, Gountouna E, Wrobel N, Harrison D, Wang B, Wu Y, Meynert A, Griffiths F, Oosthuyzen W, Kousathanas A, Moutsianas L, Yang Z, Zhai R, Zheng C, Grimes G, Beale R, Millar J, Shih B, Keating S, Zechner M, Haley C, Porteous DJ, Hayward C, Yang J, Knight J, Summers C, Shankar-Hari M, Klenerman P, Turtle L, Ho A, Moore SC, Hinds C, Horby P, Nichol A, Maslove D, Ling L, McAuley D, Montgomery H, Walsh T, Pereira A, Renieri A, GenOMICC Investigators, ISARICC Investigators, COVID-19 Human Genetics Initiative, 23andMe Investigators, BRACOVID Investigators, Gen-COVID Investigators, Shen X, Ponting CP, Fawkes A, Tenesa A, Caulfield M, Scott R, Rowan K, Murphy L, Openshaw PJM, Semple MG, Law A, Vitart V, Wilson JF, Baillie JKet al., 2021, Genetic mechanisms of critical illness in Covid-19, Nature, Vol: 591, Pages: 92-98, ISSN: 0028-0836

Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by Covid-19. Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study(GWAS) in 2244 critically ill Covid-19 patients from 208 UK intensive care units (ICUs). We identify and replicate novel genome-wide significant associations, on chr12q24.13 (rs10735079, p=1.65 [Formula: see text] 10-8) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), on chr19p13.2 (rs2109069, p=2.3 [Formula: see text] 10-12) near the gene encoding tyrosine kinase 2 (TYK2), on chr19p13.3 (rs2109069, p=3.98 [Formula: see text] 10-12) within the gene encoding dipeptidyl peptidase 9 (DPP9), and on chr21q22.1 (rs2236757, p=4.99 [Formula: see text] 10-8) in the interferon receptor gene IFNAR2. We identify potential targets for repurposing of licensed medications: using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease; transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms, and mediators of inflammatory organ damage in Covid-19. Both mechanisms may be amenable to targeted treatment with existing drugs. Large-scale randomised clinical trials will be essential before any change to clinical practice.

Journal article

Labeau SO, Afonso E, Benbenishty J, Blackwood B, Boulanger C, Brett SJ, Calvino-Gunther S, Chaboyer W, Coyer F, Deschepper M, Francois G, Honore PM, Jankovic R, Khanna AK, Llaurado-Serra M, Lin F, Rose L, Rubulotta F, Saager L, Williams G, Blot SIet al., 2021, Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study (vol 47, pg 160, 2021), Intensive Care Medicine, Vol: 47, Pages: 503-520, ISSN: 0342-4642

Journal article

Barnacle JR, Cairney G, Rainsley J, Mercuri L, Gibani MM, Cooke GS, Brett SJet al., 2021, Changes in the hospital admission profile of COVID-19 positive patients at a central London trust., Journal of Infection, Vol: 82, Pages: 159-198, ISSN: 0163-4453

Journal article

Benger JR, Lazaroo MJ, Clout M, Voss S, Black S, Brett S, Kirby K, Nolan JP, Reeves BC, Robinson M, Scott LJ, Smartt H, South A, Taylor J, Thomas M, Wordsworth S, Rogers CAet al., 2020, Randomized trial of the i-gel supraglottic airway device versus tracheal intubation during out of hospital cardiac arrest (AIRWAYS-2): Patient outcomes at three and six months, Resuscitation, Vol: 157, Pages: 74-82, ISSN: 0300-9572

AimThe AIRWAYS-2 cluster randomised controlled trial compared the i-gel supraglottic airway device (SGA) with tracheal intubation (TI) as the first advanced airway management (AAM) strategy used by Emergency Medical Service clinicians (paramedics) treating adult patients with non-traumatic out-of-hospital cardiac arrest (OHCA). It showed no difference between the two groups in the primary outcome of modified Rankin Scale (mRS) score at 30 days/hospital discharge. This paper reports outcomes to 6 months.MethodsParamedics from four ambulance services in England were randomised 1:1 to use an i-gel SGA (759 paramedics) or TI (764 paramedics) as their initial approach to AAM. Adults who had a non-traumatic OHCA and were attended by a participating paramedic were enrolled automatically under a waiver of consent. Survivors were invited to complete questionnaires at three and six months after OHCA. Outcomes were analysed using regression methods.Results767/9296 (8.3%) enrolled patients survived to 30 days/hospital discharge and 317/767 survivors (41.3%) consented and were followed-up to six months. No significant differences were found between the two treatment groups in the primary outcome measure (mRS score: 3 months: odds ratio (OR) for good recovery (i-gel/TI, OR) 0.89, 95% CI 0.69–1.14; 6 months OR 0.91, 95% CI 0.71–1.16). EQ-5D-5L scores were also similar between groups and sensitivity analyses did not alter the findings.ConclusionThere were no statistically significant differences between the TI and i-gel groups at three and six months. We therefore conclude that the initially reported finding of no significant difference between groups at 30 days/hospital discharge was sustained when the period of follow-up was extended to six months.

Journal article

Gasparini M, Khan S, Patel JM, Parekh D, Bangash MN, Stumpfle R, Shah A, Baharlo B, Soni Set al., 2020, Renal impairment and its impact on clinical outcomes in patients who are critically ill with COVID-19: a multicentre observational study, ANAESTHESIA, Vol: 76, Pages: 320-326, ISSN: 0003-2409

Journal article

Labeau SO, Afonso E, Benbenishty J, Blackwood B, Boulanger C, Brett SJ, Calvino-Gunther S, Chaboyer W, Coyer F, Deschepper M, Francois G, Honore PM, Jankovic R, Khanna AK, Llaurado-Serra M, Lin F, Rose L, Rubulotta F, Saager L, Williams G, Blot Set al., 2020, Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study, Intensive Care Medicine, Vol: 47, Pages: 160-169, ISSN: 0342-4642

PurposeIntensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients.MethodsInternational 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis.ResultsData from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score < 19, ICU stay > 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3).ConclusionPressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat.

Journal article

Gross J, Borkowski J, Brett S, 2020, Patient or family perceived deterioration in functional status and outcome after Intensive Care admission: a retrospective cohort analysis of routinely collected data, BMJ Open, Vol: 10, Pages: 1-6, ISSN: 2044-6055

Objective: To explore the association of patient or family reported functional deterioration (defined by a single question) in the preceding year, with mortality outcome for those admitted to the Intensive Care Unit (ICU).Design: Retrospective observational analysis of a routinely collected data source.Participants: Patients that were admitted to the ICU at Northwick Park and St Marks Hospitals, London North West University Healthcare NHS Trust between 1/10/2017 to 15/6/2019 were included. Patients were excluded if they had a prior ICU admission during the existing hospital episode or if information on functional deterioration could not be retrieved from either the patient or their advocate.Primary Outcomes: Mortality at the point of hospital discharge and 1 year following admission to the ICU.Results: Of the 1006 patients who were admitted to the ICU during the study period, information on functional deterioration was available for 621 patients who were included in the analysis. From these, 251 (40.4%) patients had patient or family reported functional deterioration in the preceding year, whilst 370 (59.6%) patients had a perceived stable functional baseline. Comparing the two groups, mortality was significantly higher in those who had functionally deteriorated compared to those with stable baseline function, at the point of hospital discharge (45.4% versus 25.9%; P<0.0001) and at 1 year (59.4% versus 33.0%; P<0.0001). Conclusion: Patient or family reported functional deterioration was significantly associated with higher mortality at the point of hospital discharge and at 1 year. The concept of functional deterioration in the lead up to ICU admission warrants further exploration.

Journal article

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