Imperial College London

ProfessorStephenBrett

Faculty of MedicineDepartment of Surgery & Cancer

Professor of Critical Care
 
 
 
//

Contact

 

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

 
 
//

Location

 

Hammersmith House 570Hammersmith HospitalHammersmith Campus

//

Summary

 

Publications

Publication Type
Year
to

221 results found

Corner E, Puthucheary Z, Cakiroglu A, Brett Set al., 2019, Early Functional Recovery Trajectories of Chronic Critically Ill Patients: An Observational Cohort Study, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Meiring C, Dixit A, Harris S, MacCallum NS, Brealey DA, Watkinson PJ, Jones A, Ashworth S, Beale R, Brett SJ, Singer S, Ercole Aet al., 2018, Optimal intensive care outcome prediction over time using machine learning, PLoS ONE, Vol: 13, ISSN: 1932-6203

BackgroundPrognostication is an essential tool for risk adjustment and decision making in the intensive care unit (ICU). Research into prognostication in ICU has so far been limited to data from admission or the first 24 hours. Most ICU admissions last longer than this, decisions are made throughout an admission, and some admissions are explicitly intended as time-limited prognostic trials. Despite this, temporal changes in prognostic ability during ICU admission has received little attention to date. Current predictive models, in the form of prognostic clinical tools, are typically derived from linear models and do not explicitly handle incremental information from trends. Machine learning (ML) allows predictive models to be developed which use non-linear predictors and complex interactions between variables, thus allowing incorporation of trends in measured variables over time; this has made it possible to investigate prognosis throughout an admission.Methods and findingsThis study uses ML to assess the predictability of ICU mortality as a function of time. Logistic regression against physiological data alone outperformed APACHE-II and demonstrated several important interactions including between lactate & noradrenaline dose, between lactate & MAP, and between age & MAP consistent with the current sepsis definitions. ML models consistently outperformed logistic regression with Deep Learning giving the best results. Predictive power was maximal on the second day and was further improved by incorporating trend data. Using a limited range of physiological and demographic variables, the best machine learning model on the first day showed an area under the receiver-operator characteristic curve (AUC) of 0.883 (σ = 0.008), compared to 0.846 (σ = 0.010) for a logistic regression from the same predictors and 0.836 (σ = 0.007) for a logistic regression based on the APACHE-II score. Adding information gathered on the second day of admission imp

Journal article

Gross J, Williams B, Fade P, Brett SJet al., 2018, Intensive care: balancing risk and benefit to facilitate informed decisions, British Medical Journal, Vol: 363, ISSN: 0959-8138

Journal article

Lipman J, Brett SJ, De Waele J, Osbert Cota M, Davis J, Finfer S, Glass P, Knowles S, McGuiness S, Myburgh J, Paterson D, Peake S, Rajbhandari D, Rhodes A, Roberts J, Shirwadkar C, Starr T, Taylor C, Billott L, Joel Det al., 2019, A protocol for a Phase 3 multicentre randomised controlled trial of continuous versus intermittent beta-lactam antibiotic infusion in critically ill patients with sepsis: the BLING III trial, Critical Care and Resuscitation, ISSN: 1441-2772

ackground and rationale:Beta-lactam antibiotics displaya time-dependent mechanism of action with evidence suggesting improved outcomes when administering these drugs via continuous infusion as compared with standard intermittent infusion. However, there is no phase 3randomised controlled trial (RCT) evidence to support one method of administration over another in critically ill patients with sepsis.Design and setting:BLING III is a prospective, multicentre, open, phase 3RCT to compare continuous infusion with standard intermittent infusion of beta-lactam antibiotics in critically ill patients with sepsis.The study will be conducted in approximately 70 Intensive Care Units (ICUs) in Australia, New Zealand, United Kingdom, Belgium and selected other countries from 2018 to 2021.Participants and interventions: BLING IIIwill recruit 7000 critically illpatients with sepsis being treated with one of two beta-lactam antibiotics (piperacillin-tazobactam ormeropenem) to receive the beta-lactam antibiotic by either continuous or intermittentinfusion.Main outcome measures: The primary outcome isall-cause mortality within 90 days after randomisation. Secondary outcomes are clinical cure at Day 14 post randomisation, new acquisition, colonisation or infection with a multi-resistant organism or Clostridium difficilediarrhoea up to 14 days post randomisation, all-cause ICU mortality and all-cause hospital mortality. Tertiary outcomes are ICU length of stay, hospital length of stay and duration of mechanical ventilation andduration of renal replacement therapy up to 90 days after randomisation.Results and conclusions: The BLING IIIstudy will compare the effect on 90-day mortality of beta-lactam antibiotics administered via continuous vs. intermittent infusion in 7000 critically ill patients with sepsis.

Journal article

Wong DJN, Harris SK, Moonesinghe SR, 2018, Cancelled operations: a 7-day cohort study of planned adult inpatient surgery in 245 UK National Health Service hospitals, British Journal of Anaesthesia, Vol: 121, Pages: 730-738, ISSN: 0007-0912

Journal article

Stacey M, Woods DR, Brett SJ, Britland SE, Fallowfield JL, Allsopp AJ, Delves SKet al., 2018, Heat acclimatisation blunts copeptin responses to hypertonicity from dehydrating exercise in humans, Physiological Reports, Vol: 6, ISSN: 2051-817X

Physiological Reports Volume 6, Issue 18Original Research Open AccessHeat acclimatization blunts copeptin responses to hypertonicity from dehydrating exercise in humansMichael J. Stacey David R. Woods Stephen J. Brett Sophie E. Britland Joanne L. Fallowfield Adrian J. Allsopp Simon K. DelvesFirst published: 17 September 2018https://doi.org/10.14814/phy2.13851Funding InformationThis work was supported by the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London.AboutSections AbstractAcclimatization favors greater extracellular tonicity from lower sweat sodium, yet hyperosmolality may impair thermoregulation during heat stress. Enhanced secretion or action of vasopressin could mitigate this through increased free water retention. Aims were to determine responses of the vasopressin surrogate copeptin to dehydrating exercise and investigate its relationships with tonicity during short and long‐term acclimatization. Twenty‐three participants completed a structured exercise programme following arrival from a temperate to a hot climate. A Heat Tolerance Test (HTT) was conducted on Day‐2, 6, 9 and 23, consisting of 60‐min block‐stepping at 50% VO2peak, with no fluid intake. Resting sweat [Na+] was measured by iontophoresis. Changes in body mass (sweat loss), core temperature, heart rate, osmolality (serum and urine) and copeptin and aldosterone (plasma) were measured with each Test. From Day 2 to Day 23, sweat [Na+] decreased significantly (adjusted P < 0.05) and core temperature and heart rate fell. Over the same interval, HTT‐associated excursions were increased for serum osmolality (5 [−1, 9] vs. 9 [5, 12] mosm·kg−1), did not differ for copeptin (9.6 [6.0, 15.0] vs. 7.9 [4.3, 14.7] pmol·L−1) and were reduced for aldosterone (602 [415, 946] vs. 347 [263, 537] pmol·L−1). Urine osmolality was unchanging and related consi

Journal article

Meyer J, Brett SJ, Waldmann C, 2018, Should ICU clinicians follow patients after ICU discharge? Yes, Intensive Care Medicine, Vol: 44, Pages: 1539-1541, ISSN: 0342-4642

Journal article

Wong JLC, Mason A, Gordon A, Brett Set al., 2018, Are large randomized controlled trials in severe sepsis and septic shock statistically disadvantaged by repeated inadvertent underestimates of required sample size, BMJ Open, Vol: 8, ISSN: 2044-6055

Objectives: We sought to understand why randomized controlled trials in septic shock have failed to demonstrate effectiveness in the face of improving overall outcomes for patients and seemingly promising results of early phase trials of interventions. Design: We performed a retrospective analysis of large critical care trials of severe sepsis and septic shock. Data were collected from the primary trial manuscripts, pre-published statistical plans or by direct communication with corresponding authors. Setting: Critical care randomized control trials in severe sepsis and septic shock. Participants: 14619 patients randomized in 13 trials published between 2005 to 2015, enrolling greater than 500 patients and powered to a primary outcome of mortality. Intervention: Multiple interventions including the evaluation of treatment strategies and novel therapeutics. Primary and secondary outcome measures: Our primary outcome measure was the difference between the anticipated and actual control arm mortality. Secondary analysis examined the actual effect size and the anticipated effect size employed in sample size calculation. Results: In this post-hoc analysis of 13 trials with 14 619 patients randomised, we highlight a global tendency to overestimate control arm mortality in estimating sample size (absolute difference 9.8%, 95% confidence interval, -14.7% to -5%, p<0.001). When we compared anticipated and actual effect size of a treatment there was also a substantial overestimation in proposed values (absolute difference 7.4%, 95% confidence interval -9.0% to -5.8%, p<0.0001). Conclusions: An interpretation of our results is that trials are consistently underpowered in the planning phase by employing erroneous variables to calculate a satisfactory sample size. Our analysis cannot establish if, given a larger sample size, a trial would have had a positive result. It is disappointing so many promising phase II res

Journal article

Benger JR, Kirby K, Black S, Brett SJ, Clout M, Lazaroo MJ, Nolan JP, Reeves BC, Robinson M, Scott LJ, Smartt H, South A, Stokes EA, Taylor J, Thomas M, Voss S, Wordsworth S, Rogers CAet al., 2018, Effect of a strategy of supraglottic airway device versus tracheal intubation 4 during out-of-hospital cardiac arrest on functional outcome: the AIRWAYS-2 5 randomized clinical trial, Journal of the American Medical Association, Vol: 320, Pages: 779-791, ISSN: 0098-7484

Importance The optimal approach to airway management during out-of-hospital cardiac arrest is unknown.Objective To determine whether a supraglottic airway device (SGA) is superior to tracheal intubation (TI) as the initial advanced airway management strategy in adults with nontraumatic out-of-hospital cardiac arrest.Design, Setting, and Participants Multicenter, cluster randomized clinical trial of paramedics from 4 ambulance services in England responding to emergencies for approximately 21 million people. Patients aged 18 years or older who had a nontraumatic out-of-hospital cardiac arrest and were treated by a participating paramedic were enrolled automatically under a waiver of consent between June 2015 and August 2017; follow-up ended in February 2018.Interventions Paramedics were randomized 1:1 to use TI (764 paramedics) or SGA (759 paramedics) as their initial advanced airway management strategy.Main Outcomes and Measures The primary outcome was modified Rankin Scale score at hospital discharge or 30 days after out-of-hospital cardiac arrest, whichever occurred sooner. Modified Rankin Scale score was divided into 2 ranges: 0-3 (good outcome) or 4-6 (poor outcome; 6 = death). Secondary outcomes included ventilation success, regurgitation, and aspiration.Results A total of 9296 patients (4886 in the SGA group and 4410 in the TI group) were enrolled (median age, 73 years; 3373 were women [36.3%]), and the modified Rankin Scale score was known for 9289 patients. In the SGA group, 311 of 4882 patients (6.4%) had a good outcome (modified Rankin Scale score range, 0-3) vs 300 of 4407 patients (6.8%) in the TI group (adjusted risk difference [RD], −0.6% [95% CI, −1.6% to 0.4%]). Initial ventilation was successful in 4255 of 4868 patients (87.4%) in the SGA group compared with 3473 of 4397 patients (79.0%) in the TI group (adjusted RD, 8.3% [95% CI, 6.3% to 10.2%]). However, patients randomized to receive TI were less likely to receive

Journal article

Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ, Moffatt MF, OGarra A, Openshaw PJMet al., 2018, Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza, Nature Immunology, Vol: 19, Pages: 625-635, ISSN: 1529-2916

Transcriptional profiles and host-response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole-blood mRNA signatures and concentrations of local and systemic immunological mediators in 131 adults hospitalized with influenza, from whom extensive clinical and investigational data were obtained by MOSAIC investigators. Signatures reflective of interferon-related antiviral pathways were common up to day 4 of symptoms in patients who did not require mechanical ventilator support; in those who needed mechanical ventilation, an inflammatory, activated-neutrophil and cell-stress or death (‘bacterial’) pattern was seen, even early in disease. Identifiable bacterial co-infection was not necessary for this ‘bacterial’ signature but was able to enhance its development while attenuating the early ‘viral’ signature. Our findings emphasize the importance of timing and severity in the interpretation of host responses to acute viral infection and identify specific patterns of immune-system activation that might enable the development of novel diagnostic and therapeutic tools for severe influenza.

Journal article

Vincent J-L, Lefrant J-Y, Kotfis K, Nanchal R, Martin-Loeches I, Wittebole X, Sakka SG, Pickkers P, Moreno R, Sakr Y, ICON and SOAP investigators, SOAP investigatorset al., 2018, Comparison of European ICU patients in 2012 (ICON) versus 2002 (SOAP)., Intensive Care Med, Vol: 44, Pages: 337-344

PURPOSE: To evaluate differences in the characteristics and outcomes of intensive care unit (ICU) patients over time. METHODS: We reviewed all epidemiological data, including comorbidities, types and severity of organ failure, interventions, lengths of stay and outcome, for patients from the Sepsis Occurrence in Acutely ill Patients (SOAP) study, an observational study conducted in European intensive care units in 2002, and the Intensive Care Over Nations (ICON) audit, a survey of intensive care unit patients conducted in 2012. RESULTS: We compared the 3147 patients from the SOAP study with the 4852 patients from the ICON audit admitted to intensive care units in the same countries as those in the SOAP study. The ICON patients were older (62.5 ± 17.0 vs. 60.6 ± 17.4 years) and had higher severity scores than the SOAP patients. The proportion of patients with sepsis at any time during the intensive care unit stay was slightly higher in the ICON study (31.9 vs. 29.6%, p = 0.03). In multilevel analysis, the adjusted odds of ICU mortality were significantly lower for ICON patients than for SOAP patients, particularly in patients with sepsis [OR 0.45 (0.35-0.59), p < 0.001]. CONCLUSIONS: Over the 10-year period between 2002 and 2012, the proportion of patients with sepsis admitted to European ICUs remained relatively stable, but the severity of disease increased. In multilevel analysis, the odds of ICU mortality were lower in our 2012 cohort compared to our 2002 cohort, particularly in patients with sepsis.

Journal article

Baharlo B, Bryden D, Brett SJ, 2018, Deprivation of liberty and intensive care: an update post Ferreira., J Intensive Care Soc, Vol: 19, Pages: 35-42, ISSN: 1751-1437

The right to liberty and security of the person is protected by Article 5 of the European Convention on Human Rights which has been incorporated into the Human Rights Act 1998. The 2014 Supreme Court judgment in the case commonly known as Cheshire West provided for an 'acid test' to be employed in establishing a deprivation of liberty. This 'acid test' of 'continuous supervision and not free to leave' led to concerns that patients lacking capacity being treated on an Intensive Care Unit could be at risk of a 'deprivation of liberty', if this authority was applicable to this setting. This article revisits the aftermath of Cheshire West before describing the recent legal developments around deprivation of liberty pertaining to intensive care by summarising the recent Ferreira judgments which appear for now to answer the question as to the applicability of Cheshire West in life-saving treatment.

Journal article

Harris S, Shi S, Brealey D, MacCallum NS, Denaxas S, Perez-Suarez D, Ercole A, Watkinson P, Jones A, Ashworth S, Beale R, Young D, Brett S, Singer Met al., 2018, Critical Care Health Informatics Collaborative (CCHIC): data, tools and methods for reproducible research: a multi-centre UK intensive care database, International Journal of Medical Informatics, Vol: 112, Pages: 82-89, ISSN: 1386-5056

To build and curate a linkable multi-centre database of high resolution longitudinal electronic health records (EHR) from adult Intensive Care Units (ICU). To develop a set of open-source tools to make these data ‘research ready’ while protecting patient's privacy with a particular focus on anonymisation. Materials and methods: We developed a scalable EHR processing pipeline for extracting, linking, normalising and curating and anonymising EHR data. Patient and public involvement was sought from the outset, and approval to hold these data was granted by the NHS Health Research Authority's Confidentiality Advisory Group (CAG). The data are held in a certified Data Safe Haven. We followed sustainable software development principles throughout, and defined and populated a common data model that links to other clinical areas. Results: Longitudinal EHR data were loaded into the CCHIC database from eleven adult ICUs at 5 UK teaching hospitals. From January 2014 to January 2017, this amounted to 21,930 and admissions (18,074 unique patients). Typical admissions have 70 data-items pertaining to admission and discharge, and a median of 1030 (IQR 481–2335) time-varying measures. Training datasets were made available through virtual machine images emulating the data processing environment. An open source R package, cleanEHR, was developed and released that transforms the data into a square table readily analysable by most statistical packages. A simple language agnostic configuration file will allow the user to select and clean variables, and impute missing data. An audit trail makes clear the provenance of the data at all times. Discussion: Making health care data available for research is problematic. CCHIC is a unique multi-centre longitudinal and linkable resource that prioritises patient privacy through the highest standards of data security, but also provides tools to clean, organise, and anonymise the data. We believe the development of such tools are

Journal article

Galloway M, Hegarty A, McGill S, Arulkumaran N, Brett SJ, Harrison DAet al., 2018, The effect of intensive care unit out-of-hours admission on mortalityA systematic review and meta-analysis, Critical Care Medicine, Vol: 46, Pages: 290-299, ISSN: 0090-3493

Objectives: Organizational factors are associated with outcome ofcritically ill patients and may vary by time of day and day of week.We aimed to identify the association between out-of-hours admissionto critical care and mortality.Data Sources: MEDLINE (via Ovid) and EMBASE (via Ovid).Study Selection: We performed a systematic search of the literaturefor studies on out-of-hours adult general ICU admission onpatient mortality.Data Extraction: Meta-analyses were performed and Forest plotsdrawn using RevMan software. Data are presented as odds ratios([95% CIs], p values).Data Synthesis: A total of 16 studies with 902,551 patients wereincluded in the analysis with a crude mortality of 18.2%. Fourteenstudies with 717,331 patients reported mortality rates bytime of admission and 11 studies with 835,032 patients by dayof admission. Admission to ICU at night was not associated withan increased odds of mortality compared with admissions duringthe day (odds ratio, 1.04 [0.98–1.11]; p = 0.18). However, admissionsduring the weekend were associated with an increased oddsof death compared with ICU admissions during weekdays (1.05[1.01–1.09]; p = 0.006). Increased mortality associated withweekend ICU admissions compared with weekday ICU admissionswas limited to North American countries (1.08 [1.03–1.12];p = 0.0004). The absence of a routine overnight on-site intensivistwas associated with increased mortality among weekendICU admissions compared with weekday ICU admissions (1.11[1.00–1.22]; p = 0.04) and nighttime admissions compared withdaytime ICU admissions (1.11 [1.00–1.23]; p = 0.05).Conclusions: Adjusted risk of death for ICU admission was greaterover the weekends compared with weekdays. The absence of adedicated intensivist on-site overnight may be associated withincreased mortality for acute admissions. These results need tobe interpreted in context of the organization of local healthcareresources before changes to healthcare policy are impleme

Journal article

D'Lima DM, Murray EJ, Brett SJ, 2018, Perceptions of risk and safety in the ICU: a qualitative study of cognitive processes relating to staffing, Critical Care Medicine, Vol: 46, Pages: 60-70, ISSN: 0090-3493

Objectives: The aims of this study were to 1) examine individual professionals’ perceptions of staffing risks and safe staffing in intensive care and 2) identify and examine the cognitive processes that underlie these perceptions.Design: Qualitative case study methodology with nurses, doctors, and physiotherapists.Setting: Three mixed medical and surgical adult ICUs, each on a separate hospital site within a 1,200-bed academic, tertiary London hospital group.Subjects: Forty-four ICU team members of diverse professional backgrounds and seniority.Interventions: None.Main Results: Four themes (individual, team, unit, and organizational) were identified. Individual care provision was influenced by the pragmatist versus perfectionist stance of individuals and team dynamics by the concept of an “A” team and interdisciplinary tensions. Perceptions of safety hinged around the importance of achieving a “dynamic balance” influenced by the burden of prevailing circumstances and the clinical status of patients. Organizationally, professionals’ risk perceptions affected their willingness to take personal responsibility for interactions beyond the unit.Conclusions: This study drew on cognitive research, specifically theories of cognitive dissonance, psychological safety, and situational awareness to explain how professionals’ cognitive processes impacted on ICU behaviors. Our results may have implications for relationships, management, and leadership in ICU. First, patient care delivery may be affected by professionals’ perfectionist or pragmatic approach. Perfectionists’ team role may be compromised and they may experience cognitive dissonance and subsequent isolation/stress. Second, psychological safety in a team may be improved within the confines of a perceived “A” team but diminished by interdisciplinary tensions. Third, counter intuitively, higher “situational” awareness for some individuals incre

Journal article

Sakr Y, Ferrer R, Reinhart K, Beale R, Rhodes A, Moreno R, Timsit JF, Brochard L, Thompson BT, Rezende E, Chiche JD, IC-GLOSSARI Investigators and ESICM Trials Groupet al., 2018, Correction to: The Intensive Care Global Study on Severe Acute Respiratory Infection (IC-GLOSSARI): a multicenter, multinational, 14-day inception cohort study., Intensive Care Med, Vol: 44, Pages: 144-152

In both the original publication (DOI 10.1007/s00134-015-4206-2) and the first erratum (DOI 10.1007/s00134-016-4317-4), the members of the IC-GLOSSARI Investigators and the ESICM Trials Group were provided in such a way that they could not be indexed as collaborators on PubMed. The publisher apologizes for these errors and is pleased to list the members of the groups here.

Journal article

Azoulay E, Vincent J-L, Angus DC, Arabi YM, Brochard L, Brett SJ, Citerio G, Cook DJ, Curtis JR, Dos Santos CC, Ely EW, Hall J, Halpern SD, Hart N, Hopkins RO, Iwashyna TJ, Jaber S, Latronico N, Mehta S, Needham DM, Nelson J, Puntillo K, Quintel M, Rowan K, Rubenfeld G, Van den Berghe G, Van der Hoeven J, Wunsch H, Herridge Met al., 2017, Recovery after critical illness: putting the puzzle together-a consensus of 29., Critical Care, Vol: 21, Pages: 296-296, ISSN: 1364-8535

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

Journal article

Rosculet N, Samata R, Dixit A, Harris S, MacCallum NS, Brearley DA, Watkinson PJ, Jones A, Ashworth S, Beale R, Brett SJ, Young JD, Singer M, Summers C, Ercole Aet al., 2017, USING BIG DATA TO INVESTIGATE PHYSIOLOGY: RETENTION OF CO2 DOES NOT IMPACT THE OXYGEN-HAEMOGLOBIN DISSOCIATION CURVE OF CRITICALLY ILL ADULTS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A160-A161, ISSN: 0040-6376

Conference paper

Samanta R, Dixit A, Harris S, MacCallum NS, Brearley DA, Watkinson PJ, Jones A, Ashworth S, Beale R, Brett SJ, Young JD, Singer M, Summers C, Ercole Aet al., 2017, LUNG PROTECTIVE MECHANICAL VENTILATION FOR ACUTE RESPIRATORY FAILURE IS NOT BEING IMPLEMENTED IN UK CLINICAL PRACTICE, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A81-A82, ISSN: 0040-6376

Conference paper

Stacey MJ, Delves SK, Woods DR, Britland SE, Macconnachie L, Allsopp AJ, Brett SJ, Fallowfield JLet al., 2017, Heart rate variability and plasma nephrines in the evaluation of heat acclimatisation status, European Journal of Applied Physiology, Vol: 118, Pages: 165-174, ISSN: 1439-6319

PurposeHeat adaptation (HA) is critical to performance and health in a hot environment. Transition from short-term heat acclimatisation (STHA) to long-term heat acclimatisation (LTHA) is characterised by decreased autonomic disturbance and increased protection from thermal injury. A standard heat tolerance test (HTT) is recommended for validating exercise performance status, but any role in distinguishing STHA from LTHA is unreported. The aims of this study were to (1) define performance status by serial HTT during structured natural HA, (2) evaluate surrogate markers of autonomic activation, including heart rate variability (HRV), in relation to HA status.MethodsParticipants (n = 13) were assessed by HTT (60-min block-stepping, 50% VO2peak) during STHA (Day 2, 6 and 9) and LTHA (Day 23). Core temperature (Tc) and heart rate (HR) were measured every 5 min. Sampling for HRV indices (RMSSD, LF:HF) and sympathoadrenal blood measures (cortisol, nephrines) was undertaken before and after (POST) each HTT.ResultsSignificant (P < 0.05) interactions existed for Tc, logLF:HF, cortisol and nephrines (two-way ANOVA; HTT by Day). Relative to LTHA, POST results differed significantly for Tc (Day 2, 6 and 9), HR (Day 2), logRMSSD (Day 2 and Day 6), logLF:HF (Day 2 and Day 6), cortisol (Day 2) and nephrines (Day 2 and Day 9). POST differences in HRV (Day 6 vs. 23) were + 9.9% (logRMSSD) and − 18.6% (logLF:HF).ConclusionsEarly reductions in HR and cortisol characterised STHA, whereas LTHA showed diminished excitability by Tc, HRV and nephrine measures. Measurement of HRV may have potential to aid real-time assessment of readiness for activity in the heat.

Journal article

Stacey MJ, Delves SK, Britland SE, Allsopp AJ, Brett SJ, Fallowfield JL, Woods DRet al., 2017, Copeptin reflects Physiological Strain during Thermal Stress, European Journal of Applied Physiology, Vol: 118, Pages: 75-84, ISSN: 1439-6319

PurposeTo prevent heat-related illnesses, guidelines recommend limiting core body temperature (T c) ≤ 38 °C during thermal stress. Copeptin, a surrogate for arginine vasopressin secretion, could provide useful information about fluid balance, thermal strain and health risks. It was hypothesised that plasma copeptin would rise with dehydration from occupational heat stress, concurrent with sympathoadrenal activation and reduced glomerular filtration, and that these changes would reflect T c responses.MethodsVolunteers (n = 15) were recruited from a British Army unit deployed to East Africa. During a simulated combat assault (3.5 h, final ambient temperature 27 °C), T c was recorded by radiotelemetry to differentiate volunteers with maximum T c > 38 °C versus ≤ 38 °C. Blood was sampled beforehand and afterwards, for measurement of copeptin, cortisol, free normetanephrine, osmolality and creatinine.ResultsThere was a significant (P < 0.05) rise in copeptin from pre- to post-assault (10.0 ± 6.3 vs. 16.7 ± 9.6 pmol L−1, P < 0.001). Although osmolality did not increase, copeptin correlated strongly with osmolality after the exposure (r = 0.70, P = 0.004). In volunteers with maximum T c > 38 °C (n = 8) vs ≤ 38 °C (n = 7) there were significantly greater elevations in copeptin (10.4 vs. 2.4 pmol L−1) and creatinine (10 vs. 2 μmol L−1), but no differences in cortisol, free normetanephrine or osmolality.ConclusionsChanges in copeptin reflected T c response more closely than sympathoadrenal markers or osmolality. Dynamic relationships with tonicity and kidney function may help to explain this finding. As a surrogate for integrated physiological strain during work in a field environment, copeptin assay could infor

Journal article

Hill NE, Murphy KG, Saeed S, Phadke R, Chambers D, Wilson DR, Brett SJ, Singer Met al., 2017, Impact of Ghrelin on Body Composition and Muscle Function in a Long-Term Rodent Model of Critical Illness, PLOS One, Vol: 12, ISSN: 1932-6203

BackgroundPatients with multiple injuries or sepsis requiring intensive care treatment invariably develop a catabolic state with resultant loss of lean body mass, for which there are currently no effective treatments. Recovery can take months and mortality is high. We hypothesise that treatment with the orexigenic and anti-inflammatory gastric hormone, ghrelin may attenuate the loss of body mass following critical illness and improve recovery.MethodsMale Wistar rats received an intraperitoneal injection of the fungal cell wall derivative zymosan to induce a prolonged peritonitis and consequent critical illness. Commencing at 48h after zymosan, animals were randomised to receive a continuous infusion of ghrelin or vehicle control using a pre-implanted subcutaneous osmotic mini-pump, and continued for 10 days.ResultsZymosan peritonitis induced significant weight loss and reduced food intake with a nadir at Day 2 and gradual recovery thereafter. Supra-physiologic plasma ghrelin levels were achieved in the treated animals. Ghrelin-treated rats ate more food and gained more body mass than controls. Ghrelin increased adiposity and promoted carbohydrate over fat metabolism, but did not alter total body protein, muscle strength nor muscle morphology. Muscle mass and strength remained significantly reduced in all zymosan-treated animals, even at ten days post-insult.ConclusionsContinuous infusion of ghrelin increased body mass and food intake, but did not increase muscle mass nor improve muscle function, in a long-term critical illness recovery model. Further studies with pulsatile ghrelin delivery or additional anabolic stimuli may further clarify the utility of ghrelin in survivors of critical illness.

Journal article

Balinskaite V, Bottle R, Sodhi V, Angus R, Brett S, Bennett P, Aylin Pet al., 2017, The risk of adverse pregnancy outcomes following non-obstetric surgery during pregnancy. Estimates from a retrospective cohort study of 6.5 million pregnancies, Annals of Surgery, Vol: 266, Pages: 260-266, ISSN: 1528-1140

Objective. To estimate the risk of adverse birth outcomes for women who underwent non-obstetric surgery during pregnancy compared with those who did not. Background. Previous research suggests that non-obstetric surgery occurs during 1%-2% of pregnancies. However, there is limited evidence quantifying risks to the mother or pregnancy of such surgery. Methods. We examined maternity admissions using hospital administrative data collected between 1st April 2002 and 31st March 2012 and identified pregnancies where non-obstetric surgery occurred. We used logistic regression models to determine the adjusted relative risk, attributable risk and number needed to harm of non-obstetric surgical procedures for adverse birth outcomes.Results. We identified 6,486,280 pregnancies. In 47,628 of these pregnancies, non-obstetric surgery had occurred. We found that non-obstetric surgery during pregnancy was associated with a higher risk of adverse birth outcomes, although the attributable risk was generally low. We estimated that every 287 surgical operations were associated with one additional stillbirth, every 31 operations associated with one additional preterm delivery, every 39 operations associated with one additional low birth weight baby, every 25 operations associated with one additional caesarean section, and every 50 operations associated with one additional long inpatient stay.Conclusions. Although we have no means of disentangling the effect of the surgery from the effect of the underlying condition, we found that the risk associated with non-obstetric surgery was relatively low, confirming that surgical procedures during pregnancy are generally safe. We believe that our findings improve upon previous research, and are useful reference points for any discussion of risk with prospective patients.

Journal article

D'Lima, Arnold G, Brett SJ, Bottle A, Smith A, Benn Jet al., 2017, Continuous monitoring and feedback of quality of recovery indicators for anaesthetists: A qualitative investigation of reported effects on professional behaviour, British Journal of Anaesthesia, Vol: 119, Pages: 115-124, ISSN: 1471-6771

Background: Research suggests that providing clinicians with feedback on their performance can result in professional behaviour change and improved clinical outcomes. Departments would benefit from understanding which characteristics of feedback support effective quality monitoring, professional behaviour change and service improvement. This study aimed to report the experience of anaesthetists participating in a long-term initiative to provide comprehensive personalized feedback to consultants on patient-reported quality of recovery indicators in a large London teaching hospital.Methods: Semi-structured interviews were conducted with 13 consultant anaesthetists, six surgical nursing leads, the theatre manager and the clinical coordinator for recovery. Transcripts were qualitatively analysed for themes linked to the perceived value of the initiative, its acceptability and its effects upon professional practice.Results: Analysis of qualitative data from participant interviews suggested that effective quality indicators must address areas that are within the control of the anaesthetist. Graphical data presentation, both longitudinal (personal variation over time) and comparative (peer-group distributions), was found to be preferable to summary statistics and provided useful and complementary perspectives for improvement. Developing trust in the reliability and credibility of the data through co-development of data reports with clinical input into areas such as case-mix adjustment was important for engagement. Making feedback specifically relevant to the recipient supported professional learning within a supportive and open collaborative environment.Conclusions: This study investigated the requirements for effective feedback on quality of anaesthetic care for anaesthetists, highlighting the mechanisms by which feedback may translate into improvements in practice at the individual and peer-group level.

Journal article

Reader TW, Reddy G, Brett SJ, 2017, Impossible decision? An investigation of risk trade-offs in the intensive care unit, Ergonomics, Vol: 61, Pages: 122-133, ISSN: 1366-5847

In the intensive care unit (ICU), clinicians must often make risk trade-offs on patient care. For example, on deciding whether to discharge a patient before they have fully recovered in order to create a bed for another, sicker, patient. When misjudged, these decisions can negatively influence patient outcomes: yet it can be difficult, if not impossible, for clinicians to evaluate with certainty the safest course of action. Using a vignette-based interview methodology, a naturalistic decision-making approach was utilised to study this phenomena. The decision preferences of ICU clinicians (n = 24) for two common risk trade-off scenarios were investigated. Qualitative analysis revealed the sample of clinicians to reach different, and sometimes oppositional, decision preferences. These practice variations emerged from differing analyses of risk, how decisions were ‘framed’ (e.g. philosophies on care), past experiences, and perceptions of group and organisational norms. Implications for patient safety and clinical decision-making are discussed.

Journal article

Kemp H, Bantel C, Gordon F, Brett S, PLAN, SEARCH, Laycock HCet al., 2017, Pain Assessment in INTensive care (PAINT): an observational study of physician-documented pain assessment in 45 intensive care units in the United Kingdom, Anaesthesia, Vol: 72, Pages: 737-748, ISSN: 1365-2044

Pain is a common and distressing symptom experienced by intensive care patients. Assessing pain in this environ-ment is challenging, and published guidelines have been inconsistently implemented. The Pain Assessment in INTen-sive care (PAINT) study aimed to evaluate the frequency and type of physician pain assessments with respect topublished guidelines. This observational service evaluation considered all pain and analgesia-related entries inpatients’records over a 24-h period, in 45 adult intensive care units (ICUs) in London and the South-East ofEngland. Data were collected from 750 patients, reflecting the practice of 362 physicians. Nearly two-thirds ofpatients (n=475, 64.5 95% CI 60.9–67.8%) received no physician-documented pain assessment during the 24-hstudy period. Just under one-third (n=215, 28.6 95% CI 25.5–32.0%) received no nursing-documented pain assess-ment, and over one-fifth (n=159, 21.2 95% CI 19.2–23.4)% received neither a doctor nor a nursing pain assessment.Two of the 45 ICUs used validated behavioural pain assessment tools. The likelihood of receiving a physician painassessment was affected by the following factors: the number of nursing assessments performed; whether the patientwas admitted as a surgical patient; the presence of tracheal tube or tracheostomy; and the length of stay in ICU.Physician-documented pain assessments in the majority of participating ICUs were infrequent and did not utiliserecommended behavioural pain assessment tools. Further research to identify factors influencing physician painassessment behaviour in ICU, such as human factors or cultural attitudes, is urgently needed.

Journal article

Berry M, Patel BV, Brett SJ, 2017, New consensus definitions for sepsis and septic shock: implications for treatment strategies and drug development?, Drugs, Vol: 77, Pages: 353-361, ISSN: 1179-1950

Sepsis continues to escape a precise diagnostic definition. The most recent consensus definition, termed Sepsis-3, highlights the importance of the maladaptive and potentially life threatening host response to infection. After briefly reviewing the history and epidemiology of sepsis, we go onto describe some of the challenges encountered classifying such a heterogenous disease state. In the context of these new definitions for sepsis and septic shock, we explore current as well as potentially novel therapies and conclude by mentioning some of the controversies of this most recent framework.Key points: The third international consensus definitions for Sepsis and Septic Shock take into account the latest pathophysiological understanding of sepsis, highlighting the importance of the life-threatening organ dysfunction caused by a dysregulated host response to infection.These advances in understanding the complexities of sepsis are not mirrored pharmacologically, where fluids, antibiotics and vasoactive medications continue to form the mainstay of therapy.Sepsis-3 aims to improve both the accuracy of the nomenclature of sepsis as well as improve clinical care. Important questions remain in regards to the clinical applicability of this latest framework.

Journal article

McNamee J, Gillies M, Barrett N, Agus A, Beale R, Bentley A, Bodenham A, Brett S, Brodie D, Finney S, Gordon A, Griffiths M, Harrison D, Jackson C, McDowell C, McNally C, Perkins G, Tunnicliffe W, Vuylsteke A, Walsh T, Wise M, Young D, McAuley Det al., 2016, pRotective vEntilation with veno-venouS lung assisT in respiratory failure: A protocol for a multicentre randomised controlled trial of extracorporeal carbon dioxide removal in patients with acute hypoxaemic respiratory failure, Journal of the Intensive Care Society, Vol: 18, Pages: 159-169, ISSN: 1751-1437

One of the few interventions to demonstrate improved outcomes for acute hypoxaemic respiratory failure is reducing tidal volumes when using mechanical ventilation, often termed lung protective ventilation. Veno-venous extracorporeal carbon dioxide removal (vv-ECCO2R) can facilitate reducing tidal volumes. pRotective vEntilation with veno-venouS lung assisT (REST) is a randomised, allocation concealed, controlled, open, multicentre pragmatic trial to determine the clinical and cost-effectiveness of lower tidal volume mechanical ventilation facilitated by vv-ECCO2R in patients with acute hypoxaemic respiratory failure. Patients requiring intubation and mechanical ventilation for acute hypoxaemic respiratory failure will be randomly allocated to receive either vv-ECCO2R and lower tidal volume mechanical ventilation or standard care with stratification by recruitment centre. There is a need for a large randomised controlled trial to establish whether vv-ECCO2R in acute hypoxaemic respiratory failure can allow the use of a more protective lung ventilation strategy and is associated with improved patient outcomes.

Journal article

Arulkumaran N, Harrison DA, Brett SJ, 2016, Association between day and time of admission to critical care and acute hospital outcome for unplanned admissions to adult general critical care units: cohort study exploring the ‘weekend effect’, British Journal of Anaesthesia, Vol: 118, Pages: 112-122, ISSN: 1471-6771

Background. We aimed to identify any association between day and time of admission to critical care and acute hospital outcome.Methods. We conducted a cohort study using prospectively collected data from the national clinical audit of adult critical care. We included 195 428 unplanned admissions from 212 adult general critical care units in England, Wales and Northern Ireland, between April 1, 2013 and March 31, 2015 in the analysis.Results. Hourly admission rates for unplanned admissions varied more than three-fold during the 24 h cycle. Overall acute hospital mortality was 26.8%. Before adjustment, acute hospital mortality was similar between weekends and weekdays but was significantly lower for admissions at night compared with the daytime (−3.4%, −3.8 to −3.0%; P<0.001). After adjustment for casemix, there remained no difference between weekends and weekdays (−0.0%, −0.4 to +0.3%; P=0.87) or between nighttime and daytime (−0.2%, −0.5 to +0.1%; P=0.21). Delays in admission were reported for 4.3% of admissions and were slightly more common during weekdays than weekends and in the daytime than at night. Delayed admission was associated with a small increase in acute hospital mortality, but adjusting for this did not affect the estimates of the effect of day and time of admission.Conclusions. The day of week and time of admission have no influence on patient mortality for unplanned admissions to adult general critical care units within the UK. Ways to improve critical care and hospital systems to minimize delays in admission and potentially improve outcomes need to be ascertained in future research.

Journal article

Stacey MJ, Brett S, Woods D, Jackson S, Ross Det al., 2016, Case ascertainment of heat illness in the British Army: evidence of under-reporting from analysis of Medical and Command notifications, 2009-2013, JOURNAL OF THE ROYAL ARMY MEDICAL CORPS, Vol: 162, Pages: 428-433, ISSN: 0035-8665

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: id=00360623&limit=30&person=true&page=2&respub-action=search.html