Publications
130 results found
Zhu Y, Zhou M, Jia X, et al., 2023, Inflammation Disrupts the Brain Network of Executive Function after Cardiac Surgery., Ann Surg, Vol: 277, Pages: e689-e698
OBJECTIVE: To investigate postoperative functional connectivity (FC) alterations across impaired cognitive domains and their causal relationships with systemic inflammation. BACKGROUND: Postoperative cognitive dysfunction commonly occurs after cardiac surgery, and both systemic and neuroinflammation may trigger its development. Whether FC alterations underlying deficits in specific cognitive domains after cardiac surgery are affected by inflammation remains unclear. METHODS: Seventeen patients, who underwent cardiac valve replacement, completed a neuropsychological test battery and brain MRI scan before surgery and on days 7 and 30 after surgery compared to age-matched healthy controls. Blood samples were taken for tumor necrosis factor-a and interleukin-6 measurements. Seed-to-voxel FC of the left dorsolateral prefrontal cortex (DLPFC) was examined. Bivariate correlation and linear regression models were used to determine the relationships among cognitive function, FC alterations, and cytokines. RESULTS: Executive function was significantly impaired after cardiac surgery. At day 7 follow-up, the surgical patients, compared to the controls, demonstrated significantly decreased DLPFC FC with the superior parietal lobe and attenuated negative connectivity in the default mode network, including the angular gyrus and posterior cingulate cortex. The left DLPFC enhanced the connectivity in the right DLPFC and posterior cingulate cortex, all of which were related to the increased tumor necrosis factor-a and decreased executive function up to day 7 after cardiac surgery. CONCLUSIONS: The decreased FC of executive control network and its anticorrelation with the default mode network may contribute to executive function deficits after cardiac surgery. Systemic inflammation may trigger these transient FC changes and executive function impairments.
Nagy I, Friston D, Cuddihy J, et al., 2023, Elevated 18:0 lysophosphatidylcholine contributes to the development of pain in tissue injury, Pain, Vol: 164, Pages: e103-e115, ISSN: 0304-3959
Tissue injuries, including burns, are major causes of death and morbidity worldwide. These injuries result in the release of intracellular molecules and subsequent inflammatory reactions, changing the tissues’ chemical milieu and leading to the development of persistent pain through activating pain-sensing primary sensory neurons. However, the majority of pain-inducing agents in injured tissues are unknown. Here, we report that, amongst other important metabolite changes, lysophosphatidylcholines (LPCs) including 18:0 LPC exhibit significant and consistent local burn injury-induced changes in concentration. 18:0 LPC induces immediate pain and the development of hypersensitivities to mechanical and heat stimuli through molecules including the transient receptor potential ion channel, vanilloid sub-family, member 1 and member 2 at least partly via increasing lateral pressure in the membrane. As levels of LPCs including 18:0 LPC increase in other tissue injuries, our data reveal a novel role for these lipids in injury-associated pain. These findings have high potential to improve patient care.
Al-Hindawi A, Vizcaychipi M, Demiris Y, 2022, Faster, better blink detection through curriculum learning by augmentation, ETRA '22: 2022 Symposium on Eye Tracking Research and Applications, Publisher: ACM, Pages: 1-7
Blinking is a useful biological signal that can gate gaze regression models to avoid the use of incorrect data in downstream tasks. Existing datasets are imbalanced both in frequency of class but also in intra-class difficulty which we demonstrate is a barrier for curriculum learning. We thus propose a novel curriculum augmentation scheme that aims to address frequency and difficulty imbalances implicitly which are are terming Curriculum Learning by Augmentation (CLbA).Using Curriculum Learning by Augmentation (CLbA), we achieve a state-of-the-art performance of mean Average Precision (mAP) 0.971 using ResNet-18 up from the previous state-of-the-art of mean Average Precision (mAP) of 0.757 using DenseNet-121 whilst outcompeting Curriculum Learning by Bootstrapping (CLbB) by a significant margin with improved calibration. This new training scheme thus allows the use of smaller and more performant Convolutional Neural Network (CNN) backbones fulfilling Nyquist criteria to achieve a sampling frequency of 102.3Hz. This paves the way for inference of blinking in real-time applications.
Al-Hindawi A, Vizcaychipi MP, Demiris Y, 2022, What is the patient looking at? Robust gaze-scene intersection under free-viewing conditions, 47th IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP), Publisher: IEEE, Pages: 2430-2434, ISSN: 1520-6149
Locating the user’s gaze in the scene, also known as Point of Regard (PoR) estimation, following gaze regression is important for many downstream tasks. Current techniques either require the user to wear and calibrate instruments, require significant pre-processing of the scene information, or place restrictions on user’s head movements.We propose a geometrically inspired algorithm that, despite its simplicity, provides high accuracy and O(J) performance under a variety of challenging situations including sparse depth maps, high noise, and high dynamic parallax between the user and the scene camera. We demonstrate the utility of the proposed algorithm in regressing the PoR from scenes captured in the Intensive Care Unit (ICU) at Chelsea & Westminster Hospital NHS Foundation Trust a .
Yang X, Li Z, Wang B, et al., 2022, Prognosis and antibody profiles in survivors of critical illness from COVID-19: a prospective multicentre cohort study., British Journal of Anaesthesia, Vol: 128, Pages: 491-500, ISSN: 0007-0912
BACKGROUND: There is a need to assess the long-term outcomes of survivors of critical illness from COVID-19. METHODS: Ninety-two survivors of critical illness from COVID-19 from four hospitals in Hubei Province, China participated in this prospective cohort study. Multiple characteristics, including lung function (lung volumes, diffusing capacity for carbon monoxide, chest computed tomography scores, and walking capacity); immune status (SARS-CoV-2-neutralising antibody and all subtypes of immunoglobulin (Ig) G against SARS-CoV-2, immune cells in response to ex vivo antigen peptide stimuli, and lymphocyte count and its subtypes); liver, coagulation, and kidney functions; quality of life; cognitive function; and mental status, were assessed after 3, 6, and 12 months of follow-up. RESULTS: Amongst the 92 enrolled survivors, 72 (78%) patients required mechanical ventilation. At 12 months, the predicted percentage diffusing capacity of lung for carbon monoxide was 82% (inter-quartile range [IQR]: 76-97%) with a residual volume of 77 (64-88)%. Other lung function parameters and the 6-min walk test improved gradually over time and were almost back to normal by 12 months. The titres of IgG and neutralising antibody to COVID-19 remained high at 12 months compared with those of controls who were not infected with COVID-19, although IgG titres decreased significantly from 34.0 (IQR: 23.8-74.3) to 15.0 (5.8-24.3) AU ml-1 (P<0.001), whereas neutralising antibodies decreased from 29.99 (IQR: 19.43-53.93) AU ml-1 at 6 months to 19.75 (13.1-29.8) AU ml-1 (P<0.001) at 12 months. In general, liver, kidney, physical, and mental functions also improved over time. CONCLUSIONS: Survivors of critical illness from COVID-19 show some persistent long-term impairments in lung function. However, a majority of these tests were normal by 12 months. These patients still had detectable levels of neutralising antibodies against SARS-CoV-2 and all types of IgG at 12 months, but the level
Al-Hindawi A, Vizcaychipi MP, Demiris Y, 2021, Continuous non-invasive eye tracking in intensive care, 43rd Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (IEEE EMBC), Publisher: IEEE, Pages: 1869-1873, ISSN: 1557-170X
Delirium, an acute confusional state, is a common occurrence in Intensive Care Units (ICUs). Patients who develop delirium have globally worse outcomes than those who do not and thus the diagnosis of delirium is of importance. Current diagnostic methods have several limitations leading to the suggestion of eye-tracking for its diagnosis through in-attention. To ascertain the requirements for an eye-tracking system in an adult ICU, measurements were carried out at Chelsea & Westminster Hospital NHS Foundation Trust. Clinical criteria guided empirical requirements of invasiveness and calibration methods while accuracy and precision were measured. A non-invasive system was then developed utilising a patient-facing RGB camera and a scene-facing RGBD camera. The system’s performance was measured in a replicated laboratory environment with healthy volunteers revealing an accuracy and precision that outperforms what is required while simultaneously being non-invasive and calibration-free The system was then deployed as part of CONfuSED, a clinical feasibility study where we report aggregated data from 5 patients as well as the acceptability of the system to bedside nursing staff. To the best of our knowledge, the system is the first eye-tracking systems to be deployed in an ICU for delirium monitoring.
Morton S, Lamont H, Silvey N, et al., 2021, Adult intensive care unit admissions with severe COVID-19 infection following emergency Caesarean section deliveries: a case series, Journal of the Intensive Care Society, Vol: 22, Pages: 288-299, ISSN: 1751-1437
BackgroundUK data suggest 6% of COVID-19 hospital admissions are either currently pregnant or immediately post-partum. However, the current literature suggests that if COVID-19 occurs in pregnancy, or post-partum, symptoms are mostly mild.MethodsAll COVID-19 admissions to one acute London National Health Service Foundation trust were reviewed since the beginning of the COVID-19 pandemic to 1 May 2020 to establish whether there were any pregnant or immediately post-partum admissions. Data were extracted from hospital electronic records and anonymised. Any patients admitted to adult intensive care unit had their case notes reviewed in detail and comparison made to a local risk-assessment guideline identifying patients at-risk of thromboembolic events or cytokine storms. Local hospital guidelines were followed. Patients admitted to adult intensive care unit gave written consent.ResultsA total of 24 pregnant or immediately post-partum patients with COVID-19 were admitted. Three patients required long adult intensive care unit admissions for severe single-organ respiratory failure after emergency C-sections. Two of these patients required proning (three times and eight times, respectively). All were considered medium risk for thromboembolic events but had rising D-dimers following adult intensive care unit admission, resulting in increased dosing of pharmacological thromboprophylaxis throughout their admission. All were considered low risk for a cytokine storm, and none had any significant cardiovascular or renal involvement. One patient developed a super-imposed fungal lung infection. All three patients developed delirium following cessation of sedation.ConclusionPregnant or immediately post-partum women can develop severe COVID-19 symptoms requiring prolonged adult intensive care unit admission. It is likely to be single-organ failure, but patients are at a high risk of a thromboembolic event and delirium.
Holford P, Carr AC, Zawari M, et al., 2021, Vitamin c intervention for critical covid-19: A pragmatic review of the current level of evidence, Life, Vol: 11
Severe respiratory infections are characterized by elevated inflammation and generation of reactive oxygen species (ROS) which may lead to a decrease in antioxidants such as vitamin C and a higher requirement for the vitamin. Administration of intravenous vitamin C to patients with pneumonia and sepsis appears to decrease the severity of the disease and potentially improve survival rate. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes pneumonia, sepsis and acute respiratory distress syndrome (ARDS) in severe cases, and is referred to as coronavirus disease 2019 (COVID-19). Patients with COVID-19 infection also appear to have depleted vitamin C status and require additional supplementation of vitamin C during the acute phase of the disease. To date there have been 12 vitamin C and COVID-19 trials published, including five randomised controlled trials (RCTs) and seven retrospective cohort studies. The current level of evidence from the RCTs suggests that intravenous vitamin C intervention may improve oxygenation parameters, reduce inflammatory markers, decrease days in hospital and reduce mortality, particularly in the more severely ill patients. High doses of oral vitamin C supplementation may also improve the rate of recovery in less severe cases. No adverse events have been reported in published vitamin C clinical trials in COVID-19 patients. Upcoming findings from larger RCTs will provide additional evidence on vitamin supplementation in COVID-19 patients.
Cuddihy J, Wu G, Ho L, et al., 2021, Lactate dehydrogenase activity staining demonstrates time-dependent immune cell infiltration in human ex-vivo burn-injured skin, Scientific Reports, Vol: 11, Pages: 1-12, ISSN: 2045-2322
Burn injuries constitute one of the most serious accidental injuries. Increased metabolic rate is a hallmark feature of burn injury. Visualising lactate dehydrogenase (LDH) activity has been previously used to identify metabolic activity differences, hence cell viability and burn depth in burn skin. LDH activity was visualised in injured and uninjured skin from 38 sub-acute burn patients. LDH activity aided the identification of spatially correlating immunocompetent cells in a sub-group of six patients. Desorption Electrospray Ionisation Mass Spectrometry Imaging (DESI MSI) was used to describe relative lactate and pyruvate abundance in burned and uninjured tissue. LDH activity was significantly increased in the middle and deep regions of burnt skin compared with superficial areas in burnt skin and uninjured tissue and positively correlated with post-burn time. Regions of increased LDH activity showed high pyruvate and low lactate abundance when examined with DESI-MSI. Areas of increased LDH activity exhibited cellular infiltration, including CD3 + and CD4 + T-lymphocytes and CD68 + macrophages. Our data demonstrate a steady increase in functional LDH activity in sub-acute burn wounds linked to cellular infiltration. The cell types associated are related to tissue restructuring and inflammation. This region in burn wounds is likely the focus of dysregulated inflammation and hypermetabolism.
Bruno RR, Wernly B, Kelm M, et al., 2021, Management and outcomes in critically ill nonagenarian versus octogenarian patients., BMC Geriatr, Vol: 21
BACKGROUND: Intensive care unit (ICU) patients age 90 years or older represent a growing subgroup and place a huge financial burden on health care resources despite the benefit being unclear. This leads to ethical problems. The present investigation assessed the differences in outcome between nonagenarian and octogenarian ICU patients. METHODS: We included 7900 acutely admitted older critically ill patients from two large, multinational studies. The primary outcome was 30-day-mortality, and the secondary outcome was ICU-mortality. Baseline characteristics consisted of frailty assessed by the Clinical Frailty Scale (CFS), ICU-management, and outcomes were compared between octogenarian (80-89.9 years) and nonagenarian (> 90 years) patients. We used multilevel logistic regression to evaluate differences between octogenarians and nonagenarians. RESULTS: The nonagenarians were 10% of the entire cohort. They experienced a higher percentage of frailty (58% vs 42%; p < 0.001), but lower SOFA scores at admission (6 + 5 vs. 7 + 6; p < 0.001). ICU-management strategies were different. Octogenarians required higher rates of organ support and nonagenarians received higher rates of life-sustaining treatment limitations (40% vs. 33%; p < 0.001). ICU mortality was comparable (27% vs. 27%; p = 0.973) but a higher 30-day-mortality (45% vs. 40%; p = 0.029) was seen in the nonagenarians. After multivariable adjustment nonagenarians had no significantly increased risk for 30-day-mortality (aOR 1.25 (95% CI 0.90-1.74; p = 0.19)). CONCLUSION: After adjustment for confounders, nonagenarians demonstrated no higher 30-day mortality than octogenarian patients. In this study, being age 90 years or more is no particular risk factor for an adverse outcome. This should be considered- together with illness severity and pre-existing functional capacity
Shida A, Vizcaychipi M, 2021, Burns during the epidemic, what changed?, BURNS, Vol: 47, Pages: 1217-1217, ISSN: 0305-4179
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.
Fronczek J, Polok K, de Lange DW, et al., 2021, Relationship between the Clinical Frailty Scale and short-term mortality in patients >= 80 years old acutely admitted to the ICU: a prospective cohort study, Critical Care (UK), Vol: 25, Pages: 1-9, ISSN: 1364-8535
BackgroundThe Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context.MethodsWe analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient’s age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score.ResultsThe median age in the sample of 7487 consecutive patients was 84 years (IQR 81–87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01).ConclusionKnowledge about a patient’s frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided.Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)
Haas LEM, Boumendil A, Flaatten H, et al., 2021, Frailty is associated with long-term outcome in patients with sepsis who are over 80 years old: results from an observational study in 241 European ICUs, AGE AND AGEING, Vol: 50, Pages: 1719-1727, ISSN: 0002-0729
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- Citations: 9
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
Heldt FS, Vizcaychipi MP, Peacock S, et al., 2021, Early risk assessment for COVID-19 patients from emergency department data using machine learning, Scientific Reports, Vol: 11, Pages: 1-13, ISSN: 2045-2322
Since its emergence in late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with more than 55 million reported cases and 1.3 million estimated deaths worldwide. While epidemiological and clinical characteristics of COVID-19 have been reported, risk factors underlying the transition from mild to severe disease among patients remain poorly understood. In this retrospective study, we analysed data of 879 confirmed SARS-CoV-2 positive patients admitted to a two-site NHS Trust hospital in London, England, between January 1st and May 26th, 2020, with a majority of cases occurring in March and April. We extracted anonymised demographic data, physiological clinical variables and laboratory results from electronic healthcare records (EHR) and applied multivariate logistic regression, random forest and extreme gradient boosted trees. To evaluate the potential for early risk assessment, we used data available during patients’ initial presentation at the emergency department (ED) to predict deterioration to one of three clinical endpoints in the remainder of the hospital stay: admission to intensive care, need for invasive mechanical ventilation and in-hospital mortality. Based on the trained models, we extracted the most informative clinical features in determining these patient trajectories. Considering our inclusion criteria, we have identified 129 of 879 (15%) patients that required intensive care, 62 of 878 (7%) patients needing mechanical ventilation, and 193 of 619 (31%) cases of in-hospital mortality. Our models learned successfully from early clinical data and predicted clinical endpoints with high accuracy, the best model achieving area under the receiver operating characteristic (AUC-ROC) scores of 0.76 to 0.87 (F1 scores of 0.42–0.60). Younger patient age was associated with an increased risk of receiving intensive care and ventilation, but lower risk of mortality. Clinical indicators of a patient’s oxyg
Peacock S, Cinelli M, Heldt FS, et al., 2021, COVID-19 Patient Outcome Prediction Using Selected Features from Emergency Department Data and Feed-Forward Neural Networks, Pages: 323-335, ISSN: 1867-8211
The severity of COVID-19 varies dramatically, ranging from asymptomatic infection to severe respiratory failure and death. Currently, few prognostic markers for disease outcomes exist, impairing patient triaging and treatment. Here, we train feed-forward neural networks on electronic health records of 819 confirmed SARS-CoV-2 positive patients admitted to a two-site NHS Trust hospital in London, England. To allow early risk assessment, the models ingest data collected in the emergency department (ED) to predict subsequent admission to intensive care, need for mechanical ventilation and in-hospital mortality. We apply univariate selection and recursive feature elimination to find the minimal subset of clinical variables needed for accurate prediction. Our models achieve AUC-ROC scores of 0.78 to 0.87, outperforming standard clinical risk scores. This accuracy is reached with as few as 13% of clinical variables routinely collected within the ED, which increases the practical applicability of such algorithms. Hence, state-of-the-art neural networks can predict severe COVID-19 accurately and early from a small subset of clinical variables.
Courtney A, Lignos L, Ward P, et al., 2021, Surgical Tracheostomy Outcomes in COVID-19–Positive Patients, OTO Open, Vol: 5
ObjectiveThe aim of this case series was to demonstrate that surgical tracheostomy can be undertaken safely in critically ill mechanically ventilated patients with coronavirus disease 2019 (COVID-19) and that it is an effective weaning tool.Study DesignRetrospective case series.SettingSingle academic teaching hospital in London.MethodsAll adult patients admitted to the adult intensive care unit (AICU), diagnosed with severe COVID-19 infection and requiring surgical tracheostomy between the March 10, 2020, and May 1, 2020, were included. Data collection focused upon patient demographics, AICU admission data, tracheostomy-specific data, and clinical outcomes.ResultsTwenty patients with COVID-19 underwent surgical tracheostomy. The main indication for tracheostomy was to assist in respiratory weaning. Patients had undergone mechanical ventilation for a median of 16.5 days prior to surgical tracheostomy. Tracheostomy remained in situ for a median of 12.5 days. Sixty percent of patients were decannulated at the end of the data collection period. There were no serious immediate or short-term complications. Surgical tracheostomy facilitated significant reduction in intravenous sedation at 48 hours after tracheostomy formation. There was no confirmed COVID-19 infection or reported sickness in the operating surgical or anesthetic teams.ConclusionSurgical tracheostomy has been demonstrated to be an effective weaning tool in patients with severe COVID-19 infection.
Labeau SO, Afonso E, Benbenishty J, et 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.
Vizcaychipi M, Shovlin C, McCarthy A, et al., 2020, Development and implementation of a COVID-19 near real time traffic light system in an acute hospital setting, Emergency Medicine Journal, Vol: 37, Pages: 630-636, ISSN: 1472-0205
Common causes of death in COVID-19 due to SARS-CoV-2 include thromboembolic disease, cytokine storm and adult respiratory distress syndrome (ARDS). Our aim was to develop a system for early detection of disease pattern in the emergency department (ED) that would enhance opportunities for personalised accelerated care to prevent disease progression. A single Trust’s COVID-19 response control command was established, and a reporting team with bioinformaticians was deployed to develop a real-time traffic light system to support clinical and operational teams. An attempt was made to identify predictive elements for thromboembolism, cytokine storm and ARDS based on physiological measurements and blood tests, and to communicate to clinicians managing the patient, initially via single consultants. The input variables were age, sex, and first recorded blood pressure, respiratory rate, temperature, heart rate, indices of oxygenation and C-reactive protein. Early admissions were used to refine the predictors used in the traffic lights. Of 923 consecutive patients who tested COVID-19 positive, 592 (64%) flagged at risk for thromboembolism, 241/923 (26%) for cytokine storm and 361/923 (39%) for ARDS. Thromboembolism and cytokine storm flags were met in the ED for 342 (37.1%) patients. Of the 318 (34.5%) patients receiving thromboembolism flags, 49 (5.3% of all patients) were for suspected thromboembolism, 103 (11.1%) were high-risk and 166 (18.0%) were medium-risk. Of the 89 (9.6%) who received a cytokine storm flag from the ED, 18 (2.0% of all patients) were for suspected cytokine storm, 13 (1.4%) were high-risk and 58 (6.3%) were medium-risk. Males were more likely to receive a specific traffic light flag. In conclusion, ED predictors were used to identify high proportions of COVID-19 admissions at risk of clinical deterioration due to severity of disease, enabling accelerated care targeted to those more likely to benefit. Larger prospective studies are encouraged.
Vizcaychipi M, Martins L, White J, et al., 2020, The iCareWean protocol on weaning from mechanical ventilation: A Single-blinded multi-centre randomised control trial comparing an open-loop decision support system and routine care, in the general Intensive Care Unit, BMJ Open, Vol: 10, Pages: 1-8, ISSN: 2044-6055
Introduction: Automated systems for ventilator management to date have been either fully heuristic rule-based systems or based on a combination of simple physiological models and rules. These have been shown to reduce the duration of mechanical ventilation in simple to wean patients. At present there are no published studies that evaluate the effect of systems that utilise detailed physiological descriptions of the individual patient.The BEACON Caresystem© is a model-based decision support system that utilises mathematical models of patients’ physiology in combination with models of clinical preferences to provide advice on appropriate ventilator settings. An individual physiological description may be particularly advantageous in selecting the appropriate therapy for a complex, heterogeneous, ICU patient population. Methods & Analysis: iCareWean is a single-blinded, multicentre, prospective randomised control trial evaluating management of mechanical ventilation as directed by the BEACON Caresystem© compared to that of current care, in the general intensive care setting. The trial will enrol 274 participants across multiple London NHS Intensive Care Units. The trial will utilise a primary outcome of duration of mechanical ventilation until successful extubation.Ethics & dissemination: Safety oversight will be under the direction of an independent committee of the study sponsor. Study approval was obtained from the regional ethics committee of the HRA, REC reference: 17/LO/0887. IRAS reference: 226610. Results will be disseminated through international critical care conference/symposium and publication in peer-reviewed journal.Trial Registration details: ClinicalTrials.gov under NCT03249623. This research is registered with the National Institute for Health Research (NIHR) under CPMS ID: 34831.
Vizcaychipi MP, Shovlin CL, McCarthy A, et al., 2020, Increase in COVID-19 inpatient survival following detection of Thromboembolic and Cytokine storm risk from the point of admission to hospital by a near real time Traffic-light System (TraCe-Tic), The Brazilian Journal of Infectious Diseases, Vol: 24, Pages: 412-421, ISSN: 1413-8670
IntroductionOur goal was to evaluate if traffic-light driven personalized care for COVID-19 was associated with improved survival in acute hospital settings.MethodsDischarge outcomes were evaluated before and after prospective implementation of a real-time dashboard with feedback to ward-based clinicians. Thromboembolic categories were “medium-risk” (D-dimer >1000 ng/mL or CRP >200 mg/L); “high-risk” (D-dimer >3000 ng/mL or CRP >250 mg/L) or “suspected” (D-dimer >5000 ng/mL). Cytokine storm risk was categorized by ferritin.Results939/1039 COVID-19 positive patients (median age 69 years, 563/939 (60%) male) completed hospital encounters to death or discharge by 21st May 2020. Thromboembolic flag criteria were reached by 568/939 (60.4%), including 238/275 (86.6%) of the patients who died, and 330/664 (49.7%) of the patients who survived to discharge, p < 0.0001. Cytokine storm flag criteria were reached by 212 (22.5%) of admissions, including 80/275 (29.0%) of the patients who died, and 132/664 (19.9%) of the patients who survived, p < 0.0001. The maximum thromboembolic flag discriminated completed encounter mortality (no flag: 37/371 [9.97%] died; medium-risk: 68/239 [28.5%]; high-risk: 105/205 [51.2%]; and suspected thromboembolism: 65/124 [52.4%], p < 0.0001). Flag criteria were reached by 535 consecutive COVID-19 positive patients whose hospital encounter completed before traffic-light introduction: 173/535 (32.3% [95% confidence intervals 28.0, 36.0]) died. For the 200 consecutive admissions after implementation of real-time traffic light flags, 46/200 (23.0% [95% confidence intervals 17.1–28.9]) died, p = 0.013. Adjusted for age and sex, the probability of death was 0.33 (95% confidence intervals 0.30–0.37) before traffic light implementation, 0.22 (0.17–0.27) after implementation, p < 0.001. In subgroup analyses, older patients, males, and patients with hypertension (p ≤ 0.01)
Shovlin CL, Vizcaychipi MP, 2020, Vascular inflammation and endothelial injury in SARS-CoV-2 infection: the overlooked regulatory cascades implicated by the ACE2 gene cluster, QJM: an international journal of medicine, ISSN: 1460-2393
COVID-19 has presented physicians with an unprecedented number of challenges and mortality. The basic question is why, in contrast to other "respiratory" viruses, SARS-CoV-2 infection can result in such multi-systemic, life-threatening complications and a severe pulmonary vasculopathy. It is widely known that SARS-CoV-2 uses membrane-bound angiotensin-converting enzyme 2 (ACE2) as a receptor, resulting in internalisation of the complex by the host cell. We discuss the evidence that failure to suppress coronaviral replication within 5 days results in sustained downregulation of ACE2 protein expression, and that ACE2 is under negative-feedback regulation. We then expose openly-available experimental repository data that demonstrate the gene for ACE2 lies in a novel cluster of interegulated genes on the X chromosome including PIR encoding pirin (quercetin 2,3-dioxygenase), and VEGFD encoding the predominantly lung-expressed vascular endothelial growth factor D. The five double-elite enhancer/promoters that are known to be operational, and shared read-through lncRNA transcripts, imply that ongoing SARS-CoV-2 infection will reduce host defences to reactive oxygen species, directly generate superoxide O2 - and H2O2 (a "ROS storm"), and impair pulmonary endothelial homeostasis. Published cellular responses to oxidative stress complete the loop to pathophysiology observed in severe COVID-19. Thus for patients who fail to rapidly suppress viral replication, the newly-appreciated ACE2 co-regulated cluster predicts delayed responses that would account for catastrophic deteriorations. We conclude that ACE2 homeostatic drives provide a unified understanding which should help optimise therapeutic approaches during the wait until safe, effective vaccines and antiviral therapies for SARS-CoV-2 are delivered.
Nepogodiev D, 2020, Elective surgery cancellations due to theCOVID-19 pandemic: global predictive modelling to inform surgical recovery plans, British Journal of Surgery, Vol: 107, Pages: 1440-1449, ISSN: 0007-1323
BackgroundThe COVID-19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12 weeks of peak disruption due to COVID-19.MethodsA global expert response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12 weeks of peak disruption. A Bayesian β-regression model was used to estimate 12-week cancellation rates for 190 countries. Elective surgical case-mix data, stratified by specialty and indication (surgery for cancer versus benign disease), were determined. This case mix was applied to country-level surgical volumes. The 12-week cancellation rates were then applied to these figures to calculate the total number of cancelled operations.ResultsThe best estimate was that 28 404 603 operations would be cancelled or postponed during the peak 12 weeks of disruption due to COVID-19 (2 367 050 operations per week). Most would be operations for benign disease (90·2 per cent, 25 638 922 of 28 404 603). The overall 12-week cancellation rate would be 72·3 per cent. Globally, 81·7 per cent of operations for benign conditions (25 638 922 of 31 378 062), 37·7 per cent of cancer operations (2 324 070 of 6 162 311) and 25·4 per cent of elective caesarean sections (441 611 of 1 735 483) would be cancelled or postponed. If countries increased their normal surgical volume by 20 per cent after the pandemic, it would take a median of 45 weeks to clear the backlog of operations resulting from COVID-19 disruption.ConclusionA very large number of operations will be cancelled or postponed owing to disruption caused by COVID-19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely.
Abraham-Thomas N, Vizcaychipi MP, 2020, Let's not forget our female front line, BMJ-BRITISH MEDICAL JOURNAL, Vol: 369, ISSN: 0959-535X
Shovlin C, Vizcaychipi M, 2020, COVID-19 genomic susceptibility: Definition of ACE2 variants relevant to human infection with SARS-CoV-2 in the context of ACMG/AMP Guidance, Publisher: medRxiv
BACKGROUND Mortality remains very high and unpredictable in COVID-19, with intense public protection strategies tailored to preceived risk. Males are at greater risk of severe COVID-19 complications. Genomic studies are in process to identify differences in host susceptibility to SARS-CoV-2 infection. METHODS Genomic structures were examined for the ACE2 gene that encodes angiotensin-converting enzyme 2, the obligate receptor for SARS-CoV-2. Variants in 213,158 exomes/genomes were integrated with ACE2 protein functional domains, and pathogenicity criteria from the American Society of Human Genetics and Genomics/Association for Molecular Pathology. RESULTS 483 variants were identified in the 19 exons of ACE2 on the X chromosome. All variants were rare, including nine loss-of-function (potentially SARS-CoV-2 protective) alleles present only in female heterozygotes. Unopposed variant alleles were more common in males (262/3596 [7.3%] nucleotides) than females (9/3596 [0.25%] nucleotides, p<0.0001). 37 missense variants substituted amino acids in SARS-CoV-2 interacting regions or critical domains for transmembrane ACE2 expression. Four upstream open reading frames with 31 associated variants were identified. Excepting loss-of-function alleles, variants would not meet minimum criteria for classification as Likely Pathogenic/beneficial if differential frequencies emerged in patients with COVID-19. CONCLUSIONS Males are more exposed to consequences from a single variant ACE2 allele. Common risk/beneficial alleles are unlikely in regions subject to evolutionary constraint. ACE2 upstream open reading frames may have implications for aminoglycoside use in SARS-CoV-2-infected patients. For this SARS-CoV-2-interacting protein with pre-identified functional domains, pre-emptive functional and computational studies are encouraged to accelerate interpretations of genomic variation for personalised and public health use.
Vizcaychipi M, Shovlin C, Hayes M, et al., 2020, Early detection of severe COVID-19 disease patterns define near real-time personalised care, bioseverity in males, and decelerating mortality rates., Publisher: medRxiv
BACKGROUND: COVID-19 is a global health emergency. Recent data indicate a 50% mortality rate across UK intensive care units. METHODS: A single institution, two-centre retrospective analysis following implementation of a Decision Support tool and real-time data dashboard for early detection of patients requiring personalised enhanced care, focussing particularly on respiratory rate, diastolic blood pressure, oxygenation indices, C-reactive protein, D-dimer and ferritin. Protocols differing from conventional practice included high-dose prophylactic anticoagulation for all COVID-19 positive patients and antioxidant prescription. RESULTS: By 22nd April 2020, 923 patients tested COVID-19 positive. 569 patients (61.7%) were male. The majority presented with advanced disease: interquartile ranges were C-reactive protein 44.9-179mg/L, D-dimer 1070-3802ng/L, and ferritin 261-1208μg/L. Completed case fatality rates were 25.1% [95% CI 20.0, 30.0] in females, 40.5% [95% CI 35.9, 45.0] in males. 139 patients were admitted to intensive care where current death rates are 16.2% [95% CI 3.8, 28.7] in females, 38.2% [95% CI 28.6, 47.8] in males with no trends for differences based on ethnicity. A real-time traffic lights dashboard enabled rapid assessment of patients using critical parameters to accelerate adjustments to management protocols. In total 513 (55.6%) of patients were flagged as high risk for thromboembolic disease, exceeding the numbers flagged for respiratory deteriorations (N=391, 42.4%), or cytokine storm (N=68, 7.4%). There was minimal evidence that age was associated with disease severity, but males had higher levels of all dashboard indices, particularly C-reactive protein and ferritin (p<0.0001) which displayed no relationship with age. CONCLUSIONS: Survival rates are encouraging. Protocols employed (traffic light-driven personalised care, protocolised early therapeutic anticoagulation based on D-dimer >1,000ng/L and/or CRP>200 mg/L, personalised ven
Shovlin C, Vizcaychipi M, 2020, Implications for COVID-19 triage from the ICNARC report of 2204 COVID-19 cases managed in UK adult intensive care units, Emergency Medicine Journal, Vol: 37, Pages: 332-333, ISSN: 1472-0205
Borges FK, Bhandari M, Guerra-Farfan E, et al., 2020, Accelerated surgery versus standard care in hip fracture (HIP ATTACK): an international, randomised, controlled trial, LANCET, Vol: 395, Pages: 698-708, ISSN: 0140-6736
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Kong E, Nicolaou N, Vizcaychipi MP, 2020, Hemodynamic stability of closed-loop anesthesia systems: a systematic review, MINERVA ANESTESIOLOGICA, Vol: 86, Pages: 76-87, ISSN: 0375-9393
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