Publications
281 results found
Pandolfo A, Horne R, Yogini J, et al., 2022, Understanding decisions about antibiotic prescribing in ICU: an application of the Necessity Concerns Framework, BMJ Quality and Safety, Vol: 31, Pages: 199-210, 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
Warner B, Harry A, Brett S, et al., 2022, The end is just the beginning: involvement of bereaved next of kin in qualitative research, BMJ Supportive & Palliative Care, Vol: 12, ISSN: 2045-4368
Stacey MJ, Hill N, Parsons I, et al., 2022, Relative changes in brain and kidney biomarkers with Exertional Heat Illness during a cool weather marathon, PLoS One, Vol: 17, ISSN: 1932-6203
Background:Medical personnel may find it challenging to distinguish severe Exertional Heat Illness (EHI), with attendant risks of organ-injury and longer-term sequalae, from lesser forms of incapacity associated with strenuous physical exertion. Early evidence for injury at point-of-incapacity could aid the development and application of targeted interventions to improve outcomes. We aimed to investigate whether biomarker surrogates for end-organ damage sampled at point-of-care (POC) could discriminate EHI versus successful marathon performance.Methods:Eight runners diagnosed as EHI cases upon reception to medical treatment facilities and 30 successful finishers of the same cool weather marathon (ambient temperature 8 rising to 12 ºC) were recruited. Emerging clinical markers associated with injury affecting the brain (neuron specific enolase, NSE; S100 calcium-binding protein B, S100β) and renal system (cystatin C, cysC; kidney-injury molecule-1, KIM-1; neutrophil gelatinase-associated lipocalin, NGAL), plus copeptin as a surrogate for fluid-regulatory stress, were sampled in blood upon marathon collapse/completion, as well as beforehand at rest (successful finishers only).Results:Versus successful finishers, EHI showed significantly higher NSE (10.33 [6.37, 20.00] vs. 3.17 [2.71, 3.92] ug.L-1, P<0.0001), cysC (1.48 [1.10, 1.67] vs. 1.10 [0.95, 1.21] mg.L-1, P = 0.0092) and copeptin (339.4 [77.0, 943] vs. 18.7 [7.1, 67.9] pmol.L-1, P = 0.0050). Discrimination of EHI by ROC (Area-Under-the-Curve) showed performance that was outstanding for NSE (0.97, P<0.0001) and excellent for copeptin (AUC = 0.83, P = 0.0066).Conclusions:As novel biomarker candidates for EHI outcomes in cool-weather endurance exercise, early elevations in NSE and copeptin provided sufficient discrimination to suggest utility at point-of-incapacity. Further investigation is warranted in patients exposed to greater thermal insult, followed up over a more extended period.
Look N, Voss S, Blennow Nordström E, et al., 2022, Neurocognitive function following out-of-hospital cardiac arrest: a systematic review, Resuscitation, Vol: 170, Pages: 238-246, 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.
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.
ISARIC Clinical Characterisation Group, 2021, The value of open-source clinical science in pandemic response: lessons from ISARIC., Lancet Infectious Diseases, Vol: 21, Pages: 1623-1624, ISSN: 1473-3099
Grailey K, Leon-Villapalos C, Murray E, et 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.
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.
Shah A, MacCallum N, Harris S, et 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.
Stokes E, Lazaroo M, Clout M, et 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.
Glampson B, Brittain J, Kaura A, et 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)
Billot L, Lipman J, Brett SJ, et 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.
Grailey K, Murray E, Reader T, et 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
Grailey K, Leon-Villapolos C, Murray E, et 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
Arabi Y, Gordon A, Derde L, et al., 2021, Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized control trial, Intensive Care Medicine, Vol: 47, Pages: 867-886, ISSN: 0342-4642
Purpose: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19) Methods: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir, and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ-support free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR >1 is favorable. Results: We randomized 694 patients to receive lopinavir-ritonavir (n=255), hydroxychloroquine (n=50), combination therapy (n=27) or control (n=362). The median (IQR) organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (–1 to 15), 0 (–1 to 9) and –1 (–1 to 7), respectively, compared to 6 (–1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥99.0%), and high probabilities of harm (98.0%, 99.9% and >99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). Conclusion: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.Trial registration Clinicaltrials.gov identifier: NCT02735707
Goodwin L, Samuel K, Schofield B, et 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.
Deschepper M, Labeau SO, Waegeman W, et al., 2021, Pressure injury prediction models for critically-ill patients should consider both the case-mix and local factors., Intensive Crit Care Nurs, Vol: 65
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.
Glampson B, Brittain J, Kaura A, et 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
Pandolfo A, Horne R, Jani Y, et 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
Coughlan C, Ranisz W, Leon-Villapolas C, et al., 2021, Rehabilitation after critical illness-don't overlook technological and social factors., BMJ, Vol: 373, Pages: n1403-n1403, ISSN: 1759-2151
Stephens J, Wong J, Broomhead R, et 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
Rousseau A-F, Prescott HC, Brett SJ, et 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.
Pairo-Castineira E, Clohisey S, Klaric L, et 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.
Gasparini M, Khan S, Patel JM, et al., 2021, 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
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- Citations: 24
Labeau SO, Afonso E, Benbenishty J, et 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
Mouncey PR, Richards-Belle A, Thomas K, et al., 2021, Reduced exposure to vasopressors through permissive hypotension to reduce mortality in critically ill peoble aged 65 and over; the 65 RCT, Health Technology Assessment, Vol: 25, Pages: I-114, ISSN: 1366-5278
Background:Vasopressors are administered to critical care patients to avoid hypotension, which is associated with myocardial injury, kidney injury and death. However, they work by causing vasoconstriction, which may reduce blood flow and cause other adverse effects. A mean arterial pressure target typically guides administration. An individual patient data meta-analysis (Lamontagne F, Day AG, Meade MO, Cook DJ, Guyatt GH, Hylands M, et al. Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock. Intensive Care Med 2018;44:12–21) suggested that greater exposure, through higher mean arterial pressure targets, may increase risk of death in older patients.Objective:To estimate the clinical effectiveness and cost-effectiveness of reduced vasopressor exposure through permissive hypotension (i.e. a lower mean arterial pressure target of 60–65 mmHg) in older critically ill patients.DesignA pragmatic, randomised clinical trial with integrated economic evaluation.SettingSixty-five NHS adult general critical care units.ParticipantsCritically ill patients aged ≥ 65 years receiving vasopressors for vasodilatory hypotension.InterventionsIntervention – permissive hypotension (i.e. a mean arterial pressure target of 60–65 mmHg). Control (usual care) – a mean arterial pressure target at the treating clinician’s discretion.Main outcome measures:The primary clinical outcome was 90-day all-cause mortality. The primary cost-effectiveness outcome was 90-day incremental net monetary benefit. Secondary outcomes included receipt and duration of advanced respiratory and renal support, mortality at critical care and acute hospital discharge, and questionnaire assessment of cognitive decline and health-related quality of life at 90 days and 1 year.Results:Of 2600 patients randomised, 2463 (permissive hypotension, n = 1221; usual care, n = 1242) wer
Pandolfo AM, Horne R, Brett SJ, et al., 2021, Understanding antibiotic prescribing behaviour in ICU, Publisher: SPRINGER, Pages: 290-291, ISSN: 2210-7703
Barnacle JR, Cairney G, Rainsley J, et 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
Benger JR, Lazaroo MJ, Clout M, et 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.
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