Ari Ercole | University of Cambridge (original) (raw)

Papers by Ari Ercole

PLOS ONE, Feb 15, 2023

Multilevel linear models allow flexible statistical modelling of complex data with different leve... more Multilevel linear models allow flexible statistical modelling of complex data with different levels of stratification. Identifying the most appropriate model from the large set of possible candidates is a challenging problem. In the Bayesian setting, the standard approach is a comparison of models using the model evidence or the Bayes factor. Explicit expressions for these quantities are available for the simplest linear models with unrealistic priors, but in most cases, direct computation is impossible. In practice, Markov Chain Monte Carlo approaches are widely used, such as sequential Monte Carlo, but it is not always clear how well such techniques perform. We present a method for estimation of the log model evidence, by an intermediate marginalisation over non-variance parameters. This reduces the dimensionality of any Monte Carlo sampling algorithm, which in turn yields more consistent estimates. The aim of this paper is to show how this framework fits together and works in practice, particularly on data with hierarchical structure. We illustrate this method on simulated multilevel data and on a popular dataset containing levels of radon in homes in the US state of Minnesota.

Communications physics, Jul 12, 2023

General anaesthetics are widely used for their analgesic, immobilising, and hypnotic effects. The... more General anaesthetics are widely used for their analgesic, immobilising, and hypnotic effects. The mechanisms underlying these effects remain unclear, but likely arise from alterations to cell microstructure, and potentially mechanics. Here we investigate this hypothesis using a custom experimental setup combining calcium imaging and nanoindentation to quantify the firing activity and mechanical properties of dorsal root ganglion-derived neurons exposed to a clinical concentration of 1% isoflurane gas, a halogenated ether commonly used in general anaesthesia. We found that cell viscoelasticity and functional activity are simultaneously and dynamically altered by isoflurane at different stages of exposure. Particularly, cell firing count correlated linearly with the neuronal loss tangent, the ratio of mechanical energy dissipation and storage by the cell. Our results demonstrate that anaesthetics affect cells as a whole, reconciling seemingly contradictory theories of how anaesthetics operate, and highlight the importance of considering cell mechanics in neuronal functions, anaesthesia, and clinical neuroscience in general.

Seizures

Cambridge University Press eBooks, Jun 18, 2018

Objectives: Cerebrovascular autoregulation can be monitored with a moving linear correlation of b... more Objectives: Cerebrovascular autoregulation can be monitored with a moving linear correlation of blood pressure to cerebral blood flow velocity (mean velocity index, Mx) during cardiopulmonary bypass (CPB). Vascular reactivity can be monitored with a moving linear correlation of blood pressure to cerebral blood volume trended with near-infrared spectroscopy (hemoglobin volume index, HVx). We hypothesized that the lower limits of autoregulation (LLA) and the optimal blood pressure (ABPopt) associated with the most active autoregulation could be determined by HVx in patients undergoing CPB. Methods: Adult patients (n5109) who underwent CPB for cardiac surgery had monitoring of both autoregulation (Mx) and vascular reactivity (HVx). Individual curves of Mx and HVx were constructed by placing each in 5 mmHg bins. The LLA and ABPopt for each subject were then identified by both methods and compared for agreement by correlation analysis and Bland-Altman. Results: The average LLA defined by Mx compared to HVx were comparable (66¡13 and 66¡12 mmHg). Correlation between the LLA defined by Mx and HVx was significant (Pearson r50.2867; P50.0068). The average ABPopt with the most robust autoregulation by Mx was comparable to HVx (75¡11 and 74¡13 mmHg) with significant correlation (Pearson r50.5915; P(0.0001). Discussion: Autoregulation and vascular reactivity monitoring are expected to be distinct, as flow and volume have different phasic relationships to pressure when cerebrovascular autoregulation is active. However, the two metrics have good agreement when identifying the LLA and optimal blood pressure in patients during CPB.

The Lancet Global Health, Aug 1, 2020

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in Engli... more Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre -including this research content -immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Comparative Effectiveness of Mannitol Versus Hypertonic Saline in Patients With Traumatic Brain Injury: A CENTER-TBI Study

Journal of Neurotrauma, Jul 1, 2023

Journal of Clinical Medicine, Feb 14, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

British Journal of Surgery, Jul 22, 2022

Introduction: Current assessment of perioperative risk relies on patient and surgical factors. Ho... more Introduction: Current assessment of perioperative risk relies on patient and surgical factors. However, risk stratification is imperfect and significant unwarranted variation in outcome persists. We sought to identify factors that may influence outcome, but which are under-represented in the literature. Methods: We used process mapping of stereotyped surgical pathways to identify participants for a multidisciplinary, three round Delphi across two United Kingdom hospitals. A three-round Delphi of 91 stakeholders, from 23 professional groups was conducted. Using a 5-point Likert-scale consensus was defined as a median of >3.5 or <2.5 with an interquartile range of <1.

Bio-design and manufacturing, Dec 18, 2018

Weaning from mechanical ventilation in the intensive care unit (ICU) is a complex clinical proble... more Weaning from mechanical ventilation in the intensive care unit (ICU) is a complex clinical problem and relevant for future organ engineering. Prolonged mechanical ventilation (MV) leads to a range of medical complications that increases length of stay and costs as well as contributes to morbidity and even mortality and long-term quality of life. The need to reduce MV is both clinical and economical. Artificial intelligence or machine learning (ML) methods are promising opportunities to positively influence patient outcomes. ML methods have been proposed to enhance clinical decisions processes by using the large amount of digital information generated in the ICU setting. There is a particular interest in empirical methods (such as ML) to improve management of "difficult-to-wean" patients, due to the associated costs and adverse events associated with this population. A systematic literature search was performed using the OVID, IEEEXplore, PubMed, and Web of Science databases. All publications that included (1) the application of ML to weaning from MV in the ICU and (2) a clinical outcome measurement were reviewed. A checklist to assess the study quality of medical ML publications was modified to suit the critical assessment of ML in MV weaning literature. The systematic search identified nine studies that used ML for weaning management from MV in critical care. The weaning management application areas included (1) prediction of successful spontaneous breathing trials (SBTs), (2) prediction of successful extubation, (3) prediction of arterial blood gases, and (4) ventilator setting and oxygenation-adjustment advisory systems. Seven of the nine studies scored seven out of eight on the quality index. The remaining two of the nine studies scored one out of eight on the quality index. This scoring may, in part, be explained by the publications' focus on technical novelty, and therefore focusing on issues most important to a technical audience, instead of issues most important for a systematic medical review. This review showed that only a limited number of studies have started to assess the efficacy and effectiveness of ML for MV in the ICU. However, ML has the potential to be applied to the prediction of SBT failure, extubation failure, and blood gases, and also the adjustment of ventilator and oxygenation settings. The available databases for the development of ML in this clinical area may still be inadequate. None of the reviewed studies reported on the procedure, treatment, or sedation strategy undergone by patients. Such information is unlikely to be required in a technical publication but is potentially vital to the development ML techniques that are sufficiently robust to meet the needs of the "difficult-to-wean" patient population.

Intensive Care Medicine, Jul 20, 2023

arXiv (Cornell University), Jul 5, 2022

Emergency Medicine Journal, Nov 23, 2020

The majority of EDs in England have now adopted GPED. The increase in Inside/parallel models and ... more The majority of EDs in England have now adopted GPED. The increase in Inside/parallel models and the reduction in Inside/integrated models is likely to be related to the availability of capital funding to finance structural changes to EDs so that separate GP services could be provided. Further research is required to understand the relative effectiveness of the various models of GPED identified.

Social Science Research Network, 2020

The COVID-19 pandemic is quickly spreading throughout Brazil, which is rapidly ascending the rank... more The COVID-19 pandemic is quickly spreading throughout Brazil, which is rapidly ascending the ranking of countries with the highest number of cases and deaths. A particularly unstable federal regime and fragile socioeconomic situation is likely to have contributed to the impact of the disease. Amid this crisis there is substantial concern in the possible socioeconomic, geopolitical and ethnic inequity of the impact of COVID-19 on the country's particularly diverse population. Methods We performed a cross-sectional observational study of COVID-19 hospital mortality using observational data from the SIVEP-Gripe dataset. We present descriptive statistics to quantify the COVID-19 pandemic in Brazil. We assess the importance of regional factors such as education, income and health either on a state-by-state basis or by splitting Brazil into a North and a Central-South region. Mixed-effects survival analysis was used to estimate the effects of ethnicity and comorbidity at an individual level in the context of regional variation. Findings Our results show that, compared to branco comparators, hospitalised pardo and preto Brazilians have significantly higher risk of mortality, with hazard ratios and 95% CI of 1.47 (1.33-1.58) and 1.32 (1.15-1.52), respectively. In particular, pardo ethnicity was the second most important risk factor (after age). We also found that hospitalised Brazilians in North regions tend to have more comorbidities than in the Central-South, with similar proportions between the various ethnic groups. Finally, we found that states in the North have a higher hazard ratio as compared to the Central-South, and that Rio de Janeiro obtained one of the highest hazard ratios, similar to the ones of the more underdeveloped Pernambuco and Amazonas. Interpretation Our results can be interpreted according to the interplay of two independent, but correlated, effects: i) mortality by COVID-19 increases going North (vertical effect), ii) mortality increases for the pardo and preto population (horizontal effect). We speculate that the vertical effect is driven by increasing levels of comorbidity in Northern regions where levels of socioeconomic development are lower, whereas the horizontal effect may be related to lower levels of healthcare access or availability (including intensive care) for pardo and preto Brazilians. For most states the vertical and horizontal effects are correlated giving a larger cumulative mortality. However, Rio de Janeiro was found to be an outlier to this trend: It has an ethnicity composition (horizontal effect) similar to the states in the North region, despite high levels of socioeconomic development (vertical effect). Our analysis motivates an urgent effort on the part of Brazilian authorities to consider how the national response to COVID-19 can better protect pardo and preto Brazilians as well as the population of poorer states from their higher death risk from SARS-CoV-2 infection. Funding None.

BMJ Open, Jun 1, 2020

, et al. Identification of factors associated with morbidity and postoperative length of stay in ... more , et al. Identification of factors associated with morbidity and postoperative length of stay in surgically managed chronic subdural haematoma using electronic health records: a retrospective cohort study. BMJ Open 2020;10:e037385.

Research Square (Research Square), Aug 18, 2022

Introduction: Increased intracranial pressure (ICP) is one of the most important modi able and im... more Introduction: Increased intracranial pressure (ICP) is one of the most important modi able and immediate threats to critically ill patients suffering from traumatic brain injury (TBI). Two hyperosmolar agents (HOA), mannitol and hypertonic saline (HTS) are routinely used in clinical practice to treat increased ICP. We aimed to assess whether a preference for mannitol, HTS or their combined use translated into differences in (functional) outcome. Methods: The CENTER-TBI Study is a prospective multicenter cohort study. For this study, patients with TBI, admitted to the ICU, treated with mannitol and/or HTS, aged ≥16, were included. Patients and centers were differentiated based on treatment preference with mannitol and/or HTS based on structured, data-driven criteria such as rst administered HOA at the ICU. We assessed in uence of center and patient characteristics in the choice of agent using adjusted multivariate models. Furthermore, we assessed the in uence of HOA preference on (functional) outcome using adjusted ordinal and logistic regression models, and instrumental variable analyses. Results: In total, 2056 patients were assessed. Of these, 502 (24%) patients received mannitol and/or HTS on the ICU. The rst bolus of a HOA was HTS for 287 (57%) patients, mannitol for 149 (30%) patients, and both for 66 (13%) patients. Two unreactive pupils were more common for patients receiving both (13, 21%), compared to patients receiving HTS (40, 14%), or mannitol (22, 16%). Center, rather than patient characteristics, was independently associated with the preferred choice of HOA (p-value < 0.05). ICU mortality and 6-month functional outcome were similar between patients preferably treated with mannitol compared to HTS (OR = 0.8, CI = 0.4-1.7; OR = 1.1, CI = 0.7-1.8 respectively). Patients who received both also had a similar ICU mortality and 6-month functional outcome compared to patients receiving HTS (OR = 1.9, CI = 0.7-4.9; OR = 0.7, CI = 0.3-1.6 respectively). Conclusion: We found between center variability regarding HOA preference. Moreover, we found that center is a more important driver of the choice of HOA than patient characteristics. However, our study indicates that this variability is an acceptable practice given absence of differences in outcomes associated with a speci c HOA.

Research Square (Research Square), Sep 15, 2020

Purpose: To study variation in, and clinical impact of high Therapy Intensity Level (TIL) treatme... more Purpose: To study variation in, and clinical impact of high Therapy Intensity Level (TIL) treatments for elevated intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across European Intensive Care Units (ICUs). Methods: We studied high TIL treatments (metabolic suppression, hypothermia (<35 o C), intensive hyperventilation (PaCO 2 <4 kPa), and secondary decompressive craniectomy) in patients receiving ICP monitoring in the ICU stratum of the CENTER-TBI study. A random effect logistic regression model was used to determine between-centre variation in their use. A propensity score-matched model was used to study the impact on outcome (6-months Glasgow Outcome Score-extended(GOSE)), whilst adjusting for case-mix severity, signs of brain herniation on imaging, and ICP. Results: 313 of 758 patients from 52 European centres (41%) received at least one high TIL treatment with signi cant variation between centres (median odds ratio = 2.4). Patients often transiently received high TIL therapies without escalation from lower tier treatments. 38% of patients with high TIL treatment had favourable outcomes (GOSE > 5). The use of high TIL treatment was not signi cantly associated with worse outcome (285 matched pairs, OR: 1.4, 95% CI [1.0 -2.0]). However, a sensitivity analysis excluding high TIL treatments at day 1 or use of metabolic suppression at any day did reveal a statistically signi cant association with worse outcome. Conclusion: Substantial between-centre variation in use of high TIL treatments for TBI was found and treatment escalation to higher TIL treatments were often not preceded by more conventional lower TIL treatments. The signi cant association between high TIL treatments after day 1 and worse outcomes may re ect aggressive use or unmeasured confounders or inappropriate escalation strategies. Take home message: Substantial variation was found in the use of highly intensive ICP-lowering treatments across European ICUs and a stepwise escalation strategy from lower to higher intensity level therapy is often lacking. Further research is necessary to study the impact of high therapy intensity treatments. Trial registration: The core study was registered with ClinicalTrials.

Hyperoxia and traumatic brain injury: time to stop cooking the books?

Intensive Care Medicine, Dec 2, 2022

Critical Care, Mar 4, 2020

Background: The aim of this study is to validate a previously published consensus-based quality i... more Background: The aim of this study is to validate a previously published consensus-based quality indicator set for the management of patients with traumatic brain injury (TBI) at intensive care units (ICUs) in Europe and to study its potential for quality measurement and improvement. Methods: Our analysis was based on 2006 adult patients admitted to 54 ICUs between 2014 and 2018, enrolled in the CENTER-TBI study. Indicator scores were calculated as percentage adherence for structure and process indicators and as event rates or median scores for outcome indicators. Feasibility was quantified by the completeness of the variables. Discriminability was determined by the between-centre variation, estimated with a random effect regression model adjusted for case-mix severity and quantified by the median odds ratio (MOR). Statistical uncertainty of outcome indicators was determined by the median number of events per centre, using a cut-off of 10. Results: A total of 26/42 indicators could be calculated from the CENTER-TBI database. Most quality indicators proved feasible to obtain with more than 70% completeness. Sub-optimal adherence was found for most quality indicators, ranging from 26 to 93% and 20 to 99% for structure and process indicators. Significant (p < 0.001) between-centre variation was found in seven process and five outcome indicators with MORs ranging from 1.51 to 4.14. Statistical uncertainty of outcome indicators was generally high; five out of seven had less than 10 events per centre. Conclusions: Overall, nine structures, five processes, but none of the outcome indicators showed potential for quality improvement purposes for TBI patients in the ICU. Future research should focus on implementation efforts and continuous reevaluation of quality indicators. Trial registration: The core study was registered with ClinicalTrials.gov, number NCT02210221, registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).

Acta neurochirurgica, Jun 28, 2021

Background Chronic subdural haematoma (cSDH) is a common neurosurgical pathology frequently occur... more Background Chronic subdural haematoma (cSDH) is a common neurosurgical pathology frequently occurring in older patients. The impact of population ageing on cSDH caseload has not been examined, despite relevance for health system planning. Methods This is a single-centre study from the UK. Operated cases of cSDH (n = 446) for 2015-2018 were identified. Crude and directly standardised incidence rates were calculated. Medline and EMBASE were systematically searched to identify studies reporting on the incidence of cSDH by year, so an estimate of rate of incidence change could be determined. Local incidence rates were then applied to population projections for local catchment area to estimate operated cSDH numbers at 5 yearly intervals due to shifting demographics. Results We identified nine studies presenting incidence estimates. Crude estimates for operative cases ranged from 1.3/100,000/year (1.4-2.2) to 5.3/100,000/year (4.3-6.6). When non-operated cases were included, incidence was higher: 8.2/100,000/year (6.0-11.2) to 48/100,000/year (37.7-61.1). Four pairs of studies demonstrated incidence rate increases of 200-600% over the last 50 years, but data was deemed too heterogeneous to generate formal estimate of incidence change. Local crude incidence of operated cSDH was 3.50/100,000/year (3.19-3.85). Directly standardised incidence was 1.58/100,000/year (1.26-1.90). After applying local incidence rates to population projections, case numbers were predicted to increase by 53% over the next 20 years. Conclusions The incidence of cSDH is increasing. We project a 53% increase in operative caseload within our region by 2040. These are important findings for guiding future healthcare planning. Keywords Chronic subdural haematoma • Epidemiology • Incidence • Health service planning This article is part of the Topical Collection on Neurosurgery general

Nature Medicine, Sep 12, 2022