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Traumatic brain injury (TBI) remains a leading cause of death and disability worldwide. Motivations for outcome data collection in TBI are threefold: to improve patient outcomes, to facilitate research, and to provide the means and methods for wider injury surveillance. Such data play a pivotal role in population health, and ways to increase the reliability of data collection following TBI should be pursued. As a result, technology-aided follow-up of patients with neurotrauma is on the rise; there is, therefore, a need to describe how such technologies have been used. A scoping review was conducted and reported using the PRISMA extension (PRISMA-ScR). Five electronic databases (Embase, MEDLINE, Global Health, PsycInfo, and Scopus) were searched systematically using keywords derived from the concepts of "telemedicine," "TBI," "outcome assessment," and "patient-generated health data." Forty studies described follow-up technologies (FUTs) utilizing telephones (52.5%,in =/i 21), short message service (SMS; 10%,in =/i 4), smartphones (22.5%,in =/i 9), videoconferencing (10%,in =/i 4), digital assistants (2.5%,in =/i 1), and custom devices (2.5%,in =/i 1) among cohorts of patients with TBI of varying injury severity. Where reported, clinical facilitators, remote follow-up timing and intervals between sessions, synchronicity of follow-up instances, proxy involvement, outcome measures utilized, and technology evaluation efforts are described. FUTs can aid more temporally sensitive assessments and capture fluctuating sequelae, a benefit of particular relevance to TBI cohorts. However, the evidence base surrounding FUTs remains in its infancy, particularly with respect to large samples, low- and middle-income patient cohorts, and the validation of outcome measures for deployment via such remote technology.

In a traumatically injured brain, the cerebral microdialysis technique allows continuous sampling of fluid from the brain's extracellular space. The retrieved brain fluid contains useful metabolites that indicate the brain's energy state. Assessment of these metabolites along with other parameters, such as intracranial pressure, brain tissue oxygenation, and cerebral perfusion pressure, may help inform clinical decision making, guide medical treatments, and aid in the prognostication of patient outcomes. Currently, brain metabolites are assayed on bedside analysers and results can only be achieved hourly. This is a major drawback because critical information within each hour is lost. To address this, recent advances have focussed on developing biosensing techniques for integration with microdialysis to achieve continuous online monitoring. In this review, we discuss progress in this field, focusing on various types of sensing devices and their ability to quantify specific cerebral metabolites at clinically relevant concentrations. Important points that require further investigation are highlighted, and comments on future perspectives are provided., National Institute for Health Research Invention for Innovation Awards (NIHR i4i Challenge Award and NIHR i4i Product Development Award) and the NIHR Brain Injury MedTech Co-operative. C.Z. is supported by a Research Studentship from the W.D. Armstrong Trust (Uni-versity of Cambridge). F.C.A. is supported by an NIHR i4i Product Development Award. K.L.H.C. is supported by the NIHR Biomedical Research Centre, Cambridge and by an NIHR i4i Product Development Award. P.J.H. is supported by the NIHR Biomedical Research Centre Cambridge, NIHR Senior Investigator Award, and the Royal College of Surgeons of England.

IntroductionCranioplasty is a widely practised neurosurgical procedure aimed at reconstructing a skull defect, but its impact on a patient’s rehabilitation following a traumatic brain injury (TBI) or stroke could be better understood. In addition, there are many issues that a TBI patient or the patient who had a stroke and their families may have to adapt to. Insight into some of the potential social barriers, including issues related to social engagement and cosmetic considerations, would be beneficial. Currently, little is known about how this procedure impacts a patient’s recovery, the patient’s perceptions of rehabilitation precranioplasty and postcranioplasty and the broader issues of cosmesis and social reintegration. This study hopes to understand some of these issues and therefore help inform clinicians of some of the difficulties and perceptions that patients and their relatives may have.Methods and analysisA mixed-methods study. Data will be collected through focus groups with healthcare professionals (HCPs) and semi-structured interviews with patients and their relatives, field notes, a researcher diary and a patient questionnaire. Different perspectives will be brought together through method triangulation. Patient and relative data will be analysed using interpretive phenomenological analysis, and HCPs data will be analysed thematically using deductive and inductive coding.Ethics and disseminationEthical approval has been obtained from the Wales REC 7 ethics committee (Rec ref: 19/WA/0315). There is limited literature regarding a patient’s perception of the cranioplasty process, the potential impact on rehabilitation and how this may impact their reintegration into the community. The results of this study will be presented at national brain injury conferences and published in peer-reviewed, national and international journals.

INTRODUCTION: To explore our experience of hosting the 10th Annual Neurology and Neurosurgery Interest Group-Society of British Neurological Surgeons (NANSIG-SBNS) Neurosurgery Careers Day, held virtually for the first time. METHODS: Reflective feedback and review of an international, virtual neurosurgery careers day. The authors reflect on the logistics of organizing the event, and the pre- and post-event feedback provided by delegates. Recommendations have been made on how to successfully host a virtual event. The key themes that permeated the event have been outlined and discussed in the context of the feedback received. RESULTS: The event was attended by 231 delegates from 20 countries worldwide. Knowledge of neurosurgery as a career and the application process increased after attending the careers day (4.27/5 to 4.51/5, p=0.003 and 3.12/5 to 4.31/5, p

Decompressive craniectomy (DC) is an operation where a large section of the skull is removed to accommodate brain swelling. Patients who survive will usually require subsequent reconstruction of the skull using either their own bone or an artificial prosthesis, known as cranioplasty. Cranioplasty restores skull integrity but can also improve neurological function. Standard care following DC consists of the performance of cranioplasty several months later as historically, there was a concern that earlier cranioplasty may increase the risk of infection. However, recent systematic reviews have challenged this and have demonstrated that an early cranioplasty (within three months after DC) may enhance neurological recovery. However, patients are often transferred to a rehabilitation unit following their acute index admission and before their cranioplasty. A better understanding of the pathophysiological effects of cranioplasty and the relationship of timing and complications would enable more focused patient tailored rehabilitation programs, thus maximizing the benefit following cranioplasty. This may maximise recovery potential, possibly resulting in improved functional and cognitive gains, enhancement of quality of life and potentially reducing longer-term care needs. This narrative review aims to update multi-disciplinary team regarding cranioplasty, including its history, pathophysiological consequences on recovery, complications, and important clinical considerations both in the acute and rehabilitation settings.

Following traumatic brain injury (TBI), raised cerebral lactate/pyruvate ratio (LPR) reflects impaired energy metabolism. Raised LPR correlates with poor outcome and mortality following TBI. We prospectively recruited patients with TBI requiring neurocritical care and multimodal monitoring, and utilised a tiered management protocol targeting LPR. We identified patients with persistent raised LPR despite adequate cerebral glucose and oxygen provision, which we clinically classified as cerebral 'mitochondrial dysfunction' (MD). In patients with TBI and MD, we administered disodium 2,3-13C2 succinate (12 mmol/L) by retrodialysis into the monitored region of the brain. We recovered 13C-labelled metabolites by microdialysis and utilised nuclear magnetic resonance spectroscopy (NMR) for identification and quantification.Of 33 patients with complete monitoring, 73% had MD at some point during monitoring. In 5 patients with multimodality-defined MD, succinate administration resulted in reduced LPR(-12%) and raised brain glucose(+17%). NMR of microdialysates demonstrated that the exogenous 13C-labelled succinate was metabolised intracellularly via the tricarboxylic acid cycle. By targeting LPR using a tiered clinical algorithm incorporating intracranial pressure, brain tissue oxygenation and microdialysis parameters, we identified MD in TBI patients requiring neurointensive care. In these, focal succinate administration improved energy metabolism, evidenced by reduction in LPR. Succinate merits further investigation for TBI therapy., The authors disclose receipt of the following financial support for the research, authorship, and/or publication of this article: Medical Research Council (Grant no.G1002277 ID98489) and National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme). Authors��� support: NMG���National Institute for Health Research; AA���Academy of Medical Sciences Newton Fellowship; MGS���National Institute for Health Research Biomedical Research Centre, Cambridge; IJ���Medical Research Council (Grant no.G1002277 ID 98489) and National Institute for Health Research Biomedical Research Centre, Cambridge; DKM���National Institute for Health Research Senior Investigator Awards; MJK���Cambridge Australia Oliphant Scholarship in partnership with the Cambridge Trust; PJH���National Institute for Health Research (Professorship, Biomedical Research Centre, Brain Injury MedTech Co-operative, Senior Investigator Award and the Royal College of Surgeons of England; KLHC���National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme); EPT���Swedish Brain Foundation (Hj��rnfonden), Swedish Medical Society (SLS) and Swedish Society for Medical Research (SSMF); AH���Medical Research Council/Royal College of Surgeons of England Clinical Research Training Fellowship (Grant no.G0802251), the NIHR Biomedical Research Centre and the NIHR Brain Injury MedTech Co-operative.

Objective: Shortage of general neurosurgery and specialized neurotrauma care in low resource settings is a critical setback in the national surgical plans of low and middle-income countries (LMIC). Neurotrauma fellowship programs typically exist in high-income countries (HIC), where surgeons who fulfill the requirements for positions regularly stay to practice. Due to this issue, neurosurgery residents and medical students from LMICs do not have regular access to this kind of specialized training and knowledge-hubs. The objective of this paper is to present the results of a recently established neurotrauma fellowship program for neurosurgeons of LMICs in the framework of global neurosurgery collaborations, including the involvement of specialized parallel education for neurosurgery residents and medical students.Methods: The Global Neurotrauma Fellowship (GNTF) program was inaugurated in 2015 by a multi-institutional collaboration between a HIC and an LMIC. The course organizers designed it to be a 12-month program based on adapted neurotrauma international competencies with the academic support of the Barrow Neurological Institute at Phoenix Children's Hospital and Meditech Foundation in Colombia. Since 2018, additional support from the UK, National Institute of Health Research (NIHR) Global Health Research in Neurotrauma Project from the University of Cambridge enhanced the infrastructure of the program, adding a research component in global neurosurgery and system science.Results: Eight fellows from Brazil, Venezuela, Cuba, Pakistan, and Colombia have been trained and certified via the fellowship program. The integration of international competencies and exposure to different systems of care in high-income and low-income environments creates a unique environment for training within a global neurosurgery framework. Additionally, 18 residents (Venezuela, Colombia, Ecuador, Peru, Cuba, Germany, Spain, and the USA), and ten medical students (the United Kingdom, USA, Australia, and Colombia) have also participated in elective rotations of neurotrauma and critical care during the time of the fellowship program, as well as in research projects as part of an established global surgery initiative.Conclusion: We have shown that it is possible to establish a neurotrauma fellowship program in an LMIC based on the structure of HIC formal training programs. Adaptation of the international competencies focusing on neurotrauma care in low resource settings and maintaining international mentoring and academic support will allow the participants to return to practice in their home-based countries.

Managing traumatic brain injury (TBI) patients with a cerebral perfusion pressure (CPP) near to the cerebral autoregulation (CA)-guided "optimal" CPP (CPPopt) value is associated with improved outcome and might be useful to individualize care, but has never been prospectively evaluated. This study evaluated the feasibility and safety of CA-guided CPP management in TBI patients requiring intracranial pressure monitoring and therapy (TBIicp patients). The CPPopt Guided Therapy: Assessment of Target Effectiveness (COGiTATE) parallel two-arm feasibility trial took place in four tertiary centers. TBIicp patients were randomized to either the Brain Trauma Foundation (BTF) guideline CPP target range (control group) or to the individualized CA-guided CPP targets (intervention group). CPP targets were guided by six times daily software-based alerts for up to 5 days. The primary feasibility end-point was the percentage of time with CPP concordant (±5 mm Hg) with the set CPP targets. The main secondary safety end-point was an increase in therapeutic intensity level (TIL) between the control and intervention group. Twenty-eight patients were randomized to the control and 32 patients to the intervention group. CPP in the intervention group was in the target range for 46.5% (interquartile range, 41.2-58) of the monitored time, significantly higher than the feasibility target specified in the published protocol (36%; p

ObjectivesCOVID-19 presents a risk of infection and transmission for operating theatre teams. Guidelines to protect patients and staff emerged and changed rapidly based on expert opinion and limited evidence. This paper presents the experiences and innovations developed by international surgical teams during the early stages of the pandemic to attempt to mitigate risk.DesignIn-depth, semistructured interviews were audio recorded, transcribed and analysed thematically using methods of constant comparison.Participants43 participants, including surgeons from a range of specialties (primarily general surgery, otolaryngology, neurosurgery, cardiothoracic and ophthalmology), anaesthetists and those in nursing roles.SettingThe UK, Italy, Spain, the USA, China and New Zealand between March and May 2020.ResultsSurgical teams sought to mitigate COVID-19 risks by modifying their current practice with an abundance of strategies and innovations. Communication and teamwork played an integral role in how teams adapted, although participants reflected on the challenges of having to improvise in real time. Uncertainties remained about optimal surgical practice and there were significant tensions where teams were forced to balance what was best for patients while contemplating their own safety.ConclusionsThe perceptions of risks during a pandemic such as COVID-19 can be complex and context dependent. Management of these risks in surgery must be driven by evidence‐based practice resulting from a pragmatic and novel approach to collation of global evidence. The context of surgery has changed dramatically, and surgical teams have developed a plethora of innovations. There is an urgent need for high-quality evidence to inform surgical practice that optimises the safety of both patients and healthcare professionals as the COVID-19 pandemic unfolds.

BACKGROUND: The increasing shift toward a more generalized medical undergraduate curriculum has led to limited exposure to subspecialties, including neurosurgery. The lack of standardized teaching may result in insufficient coverage of core learning outcomes. Social media (SoMe) in medical education are becoming an increasingly accepted and popular way for students to meet learning objectives outside formal medical school teaching. We delivered a series of case-based discussions (CbDs) over SoMe to attempt to meet core learning needs in neurosurgery and determine whether SoMe-based CbDs were an acceptable method of education. METHODS: Twitter was used as a medium to host 9 CbDs pertaining to common neurosurgical conditions in practice. A sequence of informative and interactive tweets were formulated before live CbDs and tweeted in progressive order. Demographic data and participant feedback were collected. RESULTS: A total of 277 participants were recorded across 9 CbDs, with 654,584 impressions generated. Feedback responses were received from 135 participants (48.7%). Participants indicated an increase of 77% in their level of knowledge after participating. Of participants, 57% (n = 77) had previous CbD experience as part of traditional medical education, with 62% (n = 84) receiving a form of medical education previously through SoMe. All participants believed that the CbDs objectives were met and would attend future sessions. Of participants, 99% (n = 134) indicated that their expectations were met. CONCLUSIONS: SoMe has been shown to be a favorable and feasible medium to host live, text-based interactive CbDs. SoMe is a useful tool for teaching undergraduate neurosurgery and is easily translatable to all domains of medicine and surgery.

Background Despite current preventative strategies, road traffic collisions (RTCs) and resultant neurotrauma remain a major problem in India. This study seeks to explore local perspectives in the context within which RTCs take place and identify potential suggestions for improving the current status. Methods Ten semi-structured interviews were carried out with purposively selected key informants from the city of Visakhapatnam, Andhra Pradesh. Participants were from one of the following categories: commissioning stakeholders; service providers; community or local patient group/advocacy group representatives. Transcripts from these interviews were analysed qualitatively using the Framework Method. Results Participants felt RTCs are a serious problem in India and a leading cause of neurotrauma. Major risk factors identified related to user behaviour such as speeding and not using personal safety equipment, and the user state, namely drink driving and underage driving. Other reported risk factors included poor infrastructure, moving obstacles on the road such as other vehicles, pedestrians and animals, overloaded vehicles and substandard safety equipment. Participants discussed how RTCs affect not only the health of the casualty, but are also a burden to the healthcare system, families, and the national economy. Although there are ongoing preventative strategies being carried out by both the government and the community, challenges to successful prevention emerged from the interviews which included resource deficiencies, inconsistent implementation, lack of appropriate action, poor governance, lack of knowledge and the mindset of the community and entities involved in prevention. Recommendations were given on how prevention of RTCs and neurotrauma might be improved, addressing the areas of education and awareness, research, the pre-hospital and trauma systems, enforcement and legislation, and road engineering, in addition to building collaborations and changing mindsets. Conclusions RTCs remain a major problem in India and a significant cause of neurotrauma. Addressing the identified gaps and shortfalls in current approaches and reinforcing collective responsibility towards road safety would be the way forward in improving prevention and reducing the burden.

In traumatic brain injury (TBI), preliminary retrospective work on signal entropy suggests an association with global outcome. The goal of this study was to provide multi-center validation of the association between multi-scale entropy (MSE) of cardiovascular and cerebral physiological signals, with six-month outcome. Using the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we selected patients with a minimum of 72 h of physiological recordings and a documented six-month Glasgow Outcome Scale Extended (GOSE) score. The 10-sec summary data for heart rate (HR), mean arterial pressure (MAP), intracranial pressure (ICP), and pulse amplitude of ICP (AMP) were derived across the first 72 h of data. The MSE complexity index (MSE-Ci) was determined for HR, MAP, ICP, and AMP, with the association between MSE and dichotomized six-month outcomes assessed using Mann-Whitney U testing and logistic regression analysis. A total of 160 patients had a minimum of 72 h of recording and a documented outcome. Decreased HR MSE-Ci (7.3 [interquartile range (IQR) 5.4 to 10.2] vs. 5.1 [IQR 3.1 to 7.0]; p = 0.002), lower ICP MSE-Ci (11.2 [IQR 7.5 to 14.2] vs. 7.3 [IQR 6.1 to 11.0]; p = 0.009), and lower AMP MSE-Ci (10.9 [IQR 8.0 to 13.7] vs. 8.7 [IQR 6.6 to 11.0]; p = 0.022), were associated with death. Similarly, lower HR MSE-Ci (8.0 [IQR 6.2 to 10.9] vs. 6.2 [IQR 3.9 to 8.7]; p = 0.003) and lower ICP MSE-Ci (11.4 [IQR 8.6 to 14.4)] vs. 9.2 [IQR 6.0 to 13.5]), were associated with unfavorable outcome. Logistic regression analysis confirmed that lower HR MSE-Ci and ICP MSE-Ci were associated with death and unfavorable outcome at six months. These findings suggest that a reduction in cardiovascular and cerebrovascular system entropy is associated with worse outcomes. Further work in the field of signal complexity in TBI multi-modal monitoring is required.

Chronic subdural hematoma is a common neurological disorder mainly affecting older people.1 It consists of a collection of blood and blood breakdown products in the intracranial subdural space that liquefies over time; the inciting event often is minor head trauma; subsequent inflammation may play a role in the pathogenesis.2 The time of onset of chronic subdural hematoma is often not known but in some instances can be presumptively dated to a head injury. The incidence of chronic subdural hematoma is increasing due to an ageing population and use of anticoagulant and antiplatelet medications.3 Chronic subdural hematoma evacuation has been projected to become the most common cranial neurosurgical operation among adults by the year 2030 in the U.S

Post-concussion syndrome (PCS) refers to a constellation of physical, cognitive, and emotional symptoms after traumatic brain injury (TBI). Despite its incidence and impact, the underlying mechanisms of PCS are unclear. We hypothesized that impaired cerebral autoregulation (CA) is a contributor. In this article, we present our protocol for non-invasively assessing CA in patients with TBI and PCS in a real-world clinical setting. A prospective, observational study was integrated into outpatient clinics at a tertiary neurosurgical center. Data points included: demographics, symptom profile (Post-Concussion Symptom Scale [PCSS]) and neuropsychological assessment (Cambridge Neuropsychological Test Automated-Battery [CANTAB]). Cerebrovascular metrics (nMxa co-efficient and the transient hyperaemic-response ratio [THRR]) were collected using transcranial Doppler (TCD), finger plethysmography, and bespoke software (ICM+). Twelve participants were initially recruited but 2 were excluded after unsuccessful insonation of the middle cerebral artery (MCA); 10 participants (5 patients with TBI, 5 healthy controls) were included in the analysis (median age 26.5 years, male to female ratio: 7:3). Median PCSS scores were 6/126 for the TBI patient sub-groups. Median CANTAB percentiles were 78 (healthy controls) and 25 (TBI). nMxa was calculated for 90% of included patients, whereas THRR was calculated for 50%. Median study time was 127.5 min and feedback (n = 6) highlighted the perceived acceptability of the study. This pilot study has demonstrated a reproducible assessment of PCS and CA metrics (non-invasively) in a real-world setting. This protocol is feasible and is acceptable to participants. By scaling this methodology, we hope to test whether CA changes are correlated with symptomatic PCS in patients post-TBI.

Highlights • pDOC patients are assessed for 2-years longitudinally with both the CRS-R and EEG. • Theta power and alpha clustering correlated strongest with changes in CRS-R scores. • EEG combined with CRS-R improved predictive power of future CRS-R scores. • Early changes in EEG outperformed early changes in CRS-R in terms of prognostic power. • Regular and repeated bedside EEG is feasible and has clinical utility for pDOC., Providing an accurate prognosis for prolonged disorder of consciousness (pDOC) patients remains a clinical challenge. Large cross-sectional studies have demonstrated the diagnostic and prognostic value of functional brain networks measured using high-density electroencephalography (hdEEG). Nonetheless, the prognostic value of these neural measures has yet to be assessed by longitudinal follow-up. We address this gap by assessing the utility of hdEEG to prognosticate long-term behavioural outcome, employing longitudinal data collected from a cohort of patients assessed systematically with resting hdEEG and the Coma Recovery Scale-Revised (CRS-R) at the bedside over a period of two years. We used canonical correlation analysis to relate clinical (including CRS-R scores combined with demographic variables) and hdEEG variables to each other. This analysis revealed that the patient’s age, and the hdEEG theta band power and alpha band connectivity, contributed most significantly to the relationship between hdEEG and clinical variables. Further, we found that hdEEG measures recorded at the time of assessment augmented clinical measures in predicting CRS-R scores at the next assessment. Moreover, the rate of hdEEG change not only predicted later changes in CRS-R scores, but also outperformed clinical measures in terms of prognostic power. Together, these findings suggest that improvements in functional brain networks precede changes in behavioural awareness in pDOC. We demonstrate here that bedside hdEEG assessments conducted at specialist nursing homes are feasible, have clinical utility, and can complement clinical knowledge and systematic behavioural assessments to inform prognosis and care.

The measurement of optic nerve sheath diameter (ONSD) has been reported as a non-invasive marker for intracranial pressure (ICP). Nevertheless, it is uncertain whether possible ONSD differences occur with age and sex in healthy and brain-injured populations. The aim of this study was to investigate the effects of sex and age on ONSD in healthy volunteers and patients with traumatic brain injury. We prospectively included 122 healthy adult volunteers (Galliera Hospital, Genova, Italy), and compared age/sex dependence of ONSD to 95 adult patients (Addenbrooke's Hospital, Cambridge, UK) with severe traumatic brain injury (TBI) requiring intubation and invasive ICP monitoring. The two groups were stratified for sex and age. Age was divided into 3 subgroups: (1) young adults: 18–44 years; (2) middle-aged adults: 45–64 years; (3) old adults: >65 years. In healthy volunteers, ONSD was significantly different between males and females [median (interquartile range): 4.2 (3.9–4.6) mm vs. 4.1 (3.6–4.2) mm (p = 0.01), respectively] and was correlated with age (R = 0.50, p < 0.0001). ONSD was significantly increased in group 3 compared to groups 2 and 1, indicating that ONSD values are higher in elderly subjects. In TBI patients, no differences in ONSD were found for sex and the correlation between ONSD and age was non-significant (R = 0.13, p = 0.20). ONSD increases with age and is significantly larger for males in healthy volunteers but not in TBI patients. Different ONSD cut-off values need not be age- or sex-adjusted for the assessment of increased ICP in TBI patients.

Pressure reactivity index (PRx) and brain tissue oxygen (PbtO2) are associated with outcome in traumatic brain injury (TBI). This study explores the relationship between PRx and PbtO2 in adult moderate/severe TBI. Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high resolution intensive care unit (ICU) sub-study cohort, we evaluated those patients with archived high-frequency digital intraparenchymal intracranial pressure (ICP) and PbtO2 monitoring data of, a minimum of 6 h in duration, and the presence of a 6 month Glasgow Outcome Scale -Extended (GOSE) score. Digital physiological signals were processed for ICP, PbtO2, and PRx, with the % time above/below defined thresholds determined. The duration of ICP, PbtO2, and PRx derangements was characterized. Associations with dichotomized 6-month GOSE (alive/dead, and favorable/unfavorable outcome; ≤ 4 = unfavorable), were assessed. A total of 43 patients were included. Severely impaired cerebrovascular reactivity was seen during elevated ICP and low PbtO2 episodes. However, most of the acute ICU physiological derangements were impaired cerebrovascular reactivity, not ICP elevations or low PbtO2 episodes. Low PbtO2 without PRx impairment was rarely seen. % time spent above PRx threshold was associated with mortality at 6 months for thresholds of 0 (area under the curve [AUC] 0.734, p = 0.003), > +0.25 (AUC 0.747, p = 0.002) and > +0.35 (AUC 0.745, p = 0.002). Similar relationships were not seen for % time with ICP >20 mm Hg, and PbtO2 < 20 mm Hg in this cohort. Extreme impairment in cerebrovascular reactivity is seen during concurrent episodes of elevated ICP and low PbtO2. However, the majority of the deranged cerebral physiology seen during the acute ICU phase is impairment in cerebrovascular reactivity, with most impairment occurring in the presence of normal PbtO2 levels. Measures of cerebrovascular reactivity appear to display the most consistent associations with global outcome in TBI, compared with ICP and PbtO2.

BACKGROUND: Drain insertion following chronic subdural haematoma (CSDH) evacuation reduces recurrence and improves outcomes. The mechanism of this improvement is uncertain. We assessed whether drains result in improved postoperative imaging, and which radiological factors are associated with recurrence and functional outcome. METHODS: A multi-centre, prospective cohort study of CSDH patients was performed between May 2013 and January 2014. Patients aged > 16 years undergoing burr hole evacuation of primary CSDH with pre- and postoperative imaging were included in this subgroup analysis. Baseline and clinical details were collected. Pre- and postoperative maximal subdural width and midline shift (MLS) along with clot density were recorded. Primary outcomes comprised mRS at discharge and symptomatic recurrence requiring re-drainage. Comparisons were made using multiple logistic regression. RESULTS: Three hundred nineteen patients were identified for inclusion. Two hundred seventy-two of 319 (85%) patients underwent drain insertion at the time of surgery versus 45/319 (14%) who did not. Twenty-nine of 272 patients who underwent drain insertion experienced recurrence (10.9%) versus 9 of 45 patients without drain insertion (20.5%; p = 0.07). Overall change in median subdural width was significantly greater in the drain versus 'no drain' groups (11 mm versus 6 mm, p < 0.01). Overall change in median midline shift (MLS) was also significantly greater in the drain group (4 mm versus 3 mm, p < 0.01). On multivariate analysis, change in maximal width and MLS were significant predictors of recurrence, although only the former remained a significant predictor for functional outcome. CONCLUSIONS: The use of subdural drains results in significantly improved postoperative imaging in burr hole evacuation of CSDH, thus providing radiological corroboration for their recommended use.

Background: The purpose of this study was to investigate if admission levels of total tau (T-tau) and β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42) could predict clinical outcome in patients with mild traumatic brain injury (mTBI). Methods: A total of 105 patients with mTBI [Glasgow Coma Scale (GCS) ≥ 13] recruited in Turku University Hospital, Turku, Finland were included in this study. Blood samples were drawn within 24 h of admission for analysis of plasma T-tau, Aβ40, and Aβ42. Patients were divided into computed tomography (CT)-positive and CT-negative groups. The outcome was assessed 6–12 months after the injury using the Extended Glasgow Outcome Scale (GOSE). Outcomes were defined as complete (GOSE 8) or incomplete (GOSE < 8) recovery. The Rivermead Post Concussion Symptoms Questionnaire (RPCSQ) was also used to assess mTBI-related symptoms. Predictive values of the biomarkers were analyzed independently, in panels and together with clinical parameters. Results: The admission levels of plasma T-tau, Aβ40, and Aβ42 were not significantly different between patients with complete and incomplete recovery. The levels of T-tau, Aβ40, and Aβ42 could poorly predict complete recovery, with areas under the receiver operating characteristic curve 0.56, 0.52, and 0.54, respectively. For the whole cohort, there was a significant negative correlation between the levels of T-tau and ordinal GOSE score (Spearman ρ = −0.231, p = 0.018). In a multivariate logistic regression model including age, GCS, duration of posttraumatic amnesia, Injury Severity Score (ISS), time from injury to sampling, and CT findings, none of the biomarkers could predict complete recovery independently or together with the other two biomarkers. Plasma levels of T-tau, Aβ40, and Aβ42 did not significantly differ between the outcome groups either within the CT-positive or CT-negative subgroups. Levels of Aβ40 and Aβ42 did not significantly correlate with outcome, but in the CT-positive subgroup, the levels of T-tau significantly correlated with ordinal GOSE score (Spearman ρ = −0.288, p = 0.035). The levels of T-tau, Aβ40, and Aβ42 were not correlated with the RPCSQ scores. Conclusions: The early levels of T-tau are correlated with the outcome in patients with mTBI, but none of the biomarkers either alone or in any combinations could predict complete recovery in patients with mTBI. © Copyright © 2020 Hossain, Mohammadian, Takala, Tenovuo, Azurmendi Gil, Frantzen, van Gils, Hutchinson, Katila, Maanpaa, Menon, Newcombe, Tallus, Hrusovsky, Wilson, Gill, Blennow, Sanchez, Zetterberg and Posti.

Failure of cerebral autoregulation has been linked to unfavorable outcome after traumatic brain injury (TBI). Preliminary evidence from a small, retrospective, single-center analysis suggests that autoregulatory dysfunction may be associated with traumatic lesion expansion, particularly for pericontusional edema. The goal of this study was to further explore these associations using prospective, multi-center data from the Collaborative European Neurotrauma Effectiveness Research in TBI (CENTER-TBI) and to further explore the relationship between autoregulatory failure, lesion progression, and patient outcome. A total of 88 subjects from the CENTER-TBI High Resolution ICU Sub-Study cohort were included. All patients had an admission computed tomography (CT) scan and early repeat scan available, as well as high-frequency neurophysiological recordings covering the between-scan interval. Using a novel, semiautomated approach at lesion segmentation, we calculated absolute changes in volume of contusion core, pericontusional edema, and extra-axial hemorrhage between the imaging studies. We then evaluated associations between cerebrovascular reactivity metrics and radiological lesion progression using mixed-model regression. Analyses were adjusted for baseline covariates and non-neurophysiological factors associated with lesion growth using multi-variate methods. Impairment in cerebrovascular reactivity was significantly associated with progression of pericontusional edema and, to a lesser degree, intraparenchymal hemorrhage. In contrast, there were no significant associations with extra-axial hemorrhage. The strongest relationships were observed between RAC-based metrics and edema formation. Pulse amplitude index showed weaker, but consistent, associations with contusion growth. Cerebrovascular reactivity metrics remained strongly associated with lesion progression after taking into account contributions from non-neurophysiological factors and mean cerebral perfusion pressure. Total hemorrhagic core and edema volumes on repeat CT were significantly larger in patients who were deceased at 6 months, and the amount of edema was greater in patients with an unfavourable outcome (Glasgow Outcome Scale-Extended 1-4). Our study suggests associations between autoregulatory failure, traumatic edema progression, and poor outcome. This is in keeping with findings from a single-center retrospective analysis, providing multi-center prospective data to support those results.

Background: Patients with traumatic brain injury (TBI) exhibit a variable and unpredictable outcome. The proteins interleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have shown predictive values for the presence of intracranial lesions. Aim: To evaluate the individual and combined outcome prediction ability of IL-10 and H-FABP, and to compare them to the more studied proteins S100β, glial fibrillary acidic protein (GFAP), and neurofilament light (NF-L), both with and without clinical predictors. Methods: Blood samples from patients with acute TBI (all severities) were collected 6 months post injury using the Glasgow Outcome Scale Extended (GOSE) score, dichotomizing patients into: (i) those with favorable (GOSE≥5)/unfavorable outcome (GOSE ≤ 4) and complete (GOSE = 8)/incomplete (GOSE ≤ 7) recovery, and (ii) patients with mild TBI (mTBI) and patients with TBIs of all severities. Results: When sensitivity was set at 95–100%, the proteins' individual specificities remained low. H-FABP showed the best specificity (%) and sensitivity (100%) in predicting complete recovery in patients with mTBI. IL-10 had the best specificity (50%) and sensitivity (96%) in identifying patients with favorable outcome in patients with TBIs of all severities. When individual proteins were combined with clinical parameters, a model including H-FABP, NF-L, and ISS yielded a specificity of 56% and a sensitivity of 96% in predicting complete recovery in patients with mTBI. In predicting favorable outcome, a model consisting IL-10, age, and TBI severity reached a specificity of 80% and a sensitivity of 96% in patients with TBIs of all severities. Conclusion: Combining novel TBI biomarkers H-FABP and IL-10 with GFAP, NF-L and S100β and clinical parameters improves outcome prediction models in TBI.

BackgroundNeurotrauma is an important global health problem. The largest cause of neurotrauma worldwide is road traffic collisions (RTCs), particularly in low- and middle-income countries (LMICs). Neurotrauma and RTCs are preventable, and many preventative interventions have been implemented over the last decades, especially in high-income countries (HICs). However, it is uncertain if these strategies are applicable globally due to variations in environment, resources, population, culture and infrastructure. Given this issue, this scoping review aims to identify, quantify and describe the evidence on approaches in neurotrauma and RTCs prevention, and ascertain contextual factors that influence their implementation in LMICs and HICs.MethodsA systematic search was conducted using five electronic databases (MEDLINE, EMBASE, CINAHL, Global Health on EBSCO host, Cochrane Database of Systematic Reviews), grey literature databases, government and non-government websites, as well as bibliographic and citation searching of selected articles. The extracted data were presented using figures, tables, and accompanying narrative summaries. The results of this review were reported using the PRISMA Extension for Scoping Reviews (PRISMA-ScR).ResultsA total of 411 publications met the inclusion criteria, including 349 primary studies and 62 reviews. More than 80% of the primary studies were from HICs and described all levels of neurotrauma prevention. Only 65 papers came from LMICs, which mostly described primary prevention, focussing on road safety. For the reviews, 41 papers (66.1%) reviewed primary, 18 tertiary (29.1%), and three secondary preventative approaches. Most of the primary papers in the reviews came from HICs (67.7%) with 5 reviews on only LMIC papers. Fifteen reviews (24.1%) included papers from both HICs and LMICs. Intervention settings ranged from nationwide to community-based but were not reported in 44 papers (10.8%), most of which were reviews. Contextual factors were described in 62 papers and varied depending on the interventions.ConclusionsThere is a large quantity of global evidence on strategies and interventions for neurotrauma and RTCs prevention. However, fewer papers were from LMICs, especially on secondary and tertiary prevention. More primary research needs to be done in these countries to determine what strategies and interventions exist and the applicability of HIC interventions in LMICs.

Background Post-traumatic hydrocephalus (PTH) is potentially under-diagnosed and under-treated, generating the need for a more efficient diagnostic tool. We aim to report CSF dynamics of patients with post-traumatic ventriculomegaly. Materials and methods We retrospectively analysed post-traumatic brain injury (TBI) patients with ventriculomegaly who had undergone a CSF infusion test. We calculated the resistance to CSF outflow (Rout), AMP (pulse amplitude of intracranial pressure, ICP), dAMP (AMPplateau-AMPbaseline) and compensatory reserve index correlation coefficient between ICP and AMP (RAP). To avoid confounding factors, included patients had to be non-decompressed or with cranioplasty > 1 month previously and Rout > 6 mmHg/min/ml. Compliance was assessed using the elasticity coefficient. We also compared infusion-tested TBI patients selected for shunting versus those not selected for shunting (consultant decision based on clinical and radiological assessment and the infusion results). Finally, we used data from a group of shunted idiopathic Normal Pressure Hydrocephalus (iNPH) patients for comparison. Results Group A consisted of 36 patients with post-traumatic ventriculomegaly and Group B of 45 iNPH shunt responders. AMP and dAMP were significantly lower in Group A than B (0.55 ± 0.39 vs 1.02 ± 0.72; p Conclusions Rout and AMP were significantly lower in PTH compared to iNPH and did not always reflect the degree of hydrocephalus or atrophy reported on CT/MRI. Compliance appears reduced in PTH.

IMPORTANCE: Ischemia is an important pathophysiological mechanism after traumatic brain injury (TBI), but its incidence and spatiotemporal patterns are poorly characterized. OBJECTIVE: To comprehensively characterize the spatiotemporal changes in cerebral physiology after TBI. DESIGN, SETTING, AND PARTICIPANTS: This single-center cohort study uses 15oxygen positron emission tomography data obtained in a neurosciences critical care unit from February 1998 through July 2014 and analyzed from April 2018 through August 2019. Patients with TBI requiring intracranial pressure monitoring and control participants were recruited. EXPOSURES: Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen metabolism (CMRO2), and oxygen extraction fraction. MAIN OUTCOMES AND MEASURES: Ratios (CBF/CMRO2 and CBF/CBV) were calculated. Ischemic brain volume was compared with jugular venous saturation and brain tissue oximetry. RESULTS: A total of 68 patients with TBI and 27 control participants were recruited. Results from 1 patient with TBI and 7 health volunteers were excluded. Sixty-eight patients with TBI (13 female [19%]; median [interquartile range (IQR)] age, 29 [22-47] years) underwent 90 studies at early (day 1 [n = 17]), intermediate (days 2-5 [n = 54]), and late points (days 6-10 [n = 19]) and were compared with 20 control participants (5 female [25%]; median [IQR] age, 43 [31-47] years). The global CBF and CMRO2 findings for patients with TBI were less than the ranges for control participants at all stages (median [IQR]: CBF, 26 [22-30] mL/100 mL/min vs 38 [29-49] mL/100 mL/min; P < .001; CMRO2, 62 [55-71] μmol/100 mL/min vs 131 [101-167] μmol/100 mL/min; P < .001). Early CBF reductions showed a trend of high oxygen extraction fraction (suggesting classical ischemia), but this was inconsistent at later phases. Ischemic brain volume was elevated even in the absence of intracranial hypertension and highest at less than 24 hours after TBI (median [IQR], 36 [10-82] mL), but many patients showed later increases (median [IQR] 6-10 days after TBI, 24 [4-42] mL; across all points: patients, 10 [5-39] mL vs control participants, 1 [0-3] mL; P < 001). Ischemic brain volume was a poor indicator of jugular venous saturation and brain tissue oximetry. Patients' CBF/CMRO2 ratio was higher than controls (median [IQR], 0.42 [0.35-0.49] vs 0.3 [0.28-0.33]; P < .001) and their CBF/CBV ratio lower (median [IQR], 7.1 [6.4-7.9] vs 12.3 [11.0-14.0]; P < .001), suggesting abnormal flow-metabolism coupling and vascular reactivity. Patients' CBV was higher than controls (median [IQR], 3.7 [3.4-4.1] mL/100 mL vs 3.0 [2.7-3.6] mL/100 mL; P < .001); although values were lower in patients with intracranial hypertension, these were still greater than controls (median [IQR], 3.7 [3.2-4.0] vs 3.0 [2.7-3.6] mL/100 mL; P = .002), despite more profound reductions in partial pressure of carbon dioxide (median [IQR], 4.3 [4.1-4.6] kPa vs 4.7 [4.3-4.9] kPa; P = .001). CONCLUSIONS AND RELEVANCE: Ischemia is common early, detectable up to 10 days after TBI, possible without intracranial hypertension, and inconsistently detected by jugular or brain tissue oximetry. There is substantial between-patient and within-patient pathophysiological heterogeneity; ischemia and hyperemia commonly coexist, possibly reflecting abnormalities in flow-metabolism coupling. Increased CBV may contribute to intracranial hypertension but can coexist with abnormal CBF/CBV ratios. These results emphasize the need to consider cerebrovascular pathophysiological complexity when managing patients with TBI.

Neuroinflammation has been shown to mediate the pathophysiological response following traumatic brain injury (TBI). Accumulating evidence implicates astrocytes as key immune cells within the central nervous system (CNS), displaying both pro- and anti-inflammatory properties. The aim of this study was to investigate how in vitro human astrocyte cultures respond to cytokines across a concentration range that approximates the aftermath of human TBI. To this end, enriched cultures of human induced pluripotent stem cell (iPSC)-derived astrocytes were exposed to interleukin-1β (IL-1β) (1–10,000 pg/mL), IL-4 (1–10,000 pg/mL), IL-6 (100–1,000,000 pg/mL), IL-10 (1–10,000 pg/mL) and tumor necrosis factor (TNF)-α (1–10,000 pg/mL). After 1, 24, 48 and 72 h, cultures were fixed and immunolabeled, and the secretome/supernatant was analyzed at 24, 48, and 72 h using a human cytokine/chemokine 39-plex Luminex assay. Data were compared to previous in vitro studies of neuronal cultures and clinical TBI studies. The secretome revealed concentration-, time- and/or both concentration- and time-dependent production of downstream cytokines (29, 21, and 17 cytokines, respectively, p

Objective: More than 5 billion individuals lack access to essential surgical care. Neurosurgical care is especially limited in low-income countries (LICs). Studies describing neurosurgical care in LICs are critical for understanding global disparities in access to neurosurgical procedures. To better understand these disparities, we conducted a systematic review of the literature identifying neurosurgical patients in LICs. Methods: MEDLINE (PubMed), Embase (embase.com), and Cochrane Library (Wiley) databases were systematically searched to retrieve studies describing neurosurgical care in LICs as defined by the World Bank Country and Lending Groups income classification. All databases were searched from their inception; no date or language limits were applied. All the articles were blindly reviewed by 2 individuals. Data from eligible studies were extracted and summarized. Results: Of the 4387 citations screened, 154 studies met inclusion criteria. The number of publications substantially increased over the study period, with 49% (n = 76) of studies published in the last 5 years. Twenty-six percent (n = 40) of studies had a first author, and 30% (n = 46) had a senior author, affiliated with a country different from the LIC of study. The most common neurosurgical diagnosis was traumatic brain injury (24%, n = 37), followed by hydrocephalus (26%, n = 40), and neoplastic intracranial mass (10%, n = 16). Of LICs, 43% (n = 15/35) had no published neurosurgical literature. Conclusions: There is a significant deficit in the literature on neurosurgical care in LICs. Efforts must focus on supporting research initiatives in LICs to improve publication bias and understand disparities in access to neurosurgical care in the lowest-resource countries. Key words: Global health, Global neurosurgery, Hydrocephalus, Literature review, Low-income countries, Research, Traumatic brain injury

Cerebral microdialysis (CMD) is used in severe traumatic brain injury (TBI) in order to recover metabolites in brain extracellular fluid (ECF). To recover larger proteins and avoid fluid loss, albumin supplemented perfusion fluid (PF) has been utilized, but because of regulatory changes in the European Union, this is no longer practicable. The aim with this study was to see whether fluid, absolute (AR), and relative (RR) recovery for the novel carrier, Dextran 500, was better than conventional PF for a range of cytokines and chemokines. An in vitro setup mimicking conditions observed in the neurocritical care of TBI patients was used, utilizing 100-kDa molecular-weight cut-off CMD catheters inserted through a triple-lumen bolt cranial access device into an external solution with diluted cytokine standards in known concentrations for 48 h (divided into 6-h epochs). Samples were run on a 39-plex Luminex (Luminex Corporation, Austin, TX) assay to assess cytokine concentrations. We found that fluid recovery was inadequate in 50% of epochs with conventional PF, whereas Dextran PF overcame this limitation. The AR was higher in the Dextran PF samples for a majority of cytokines, and RR was significantly increased for macrophage colony-stimulating factor and transforming growth factor-alpha. In summary, Dextran PF improved fluid and cytokine recovery as compared to conventional PF and is a suitable alternative to albumin supplemented PF for protein microdialysis.

Background: The incidence of chronic subdural haematoma (CSDH) is increasing. Although surgery remains the mainstay of management for symptomatic patients, uncertainty remains regarding the role of steroids. Hence, the Dex-CSDH trial was launched in the UK in 2015 aiming to determine whether, compared to placebo, dexamethasone can improve the six month functional outcome of patients with symptomatic CSDH by reducing the rate of surgical intervention and recurrence rate. Methods and design: Dex-CSDH is a multi-centre, pragmatic, parallel group, double-blind, randomised trial assessing the clinical utility of a two-week course of dexamethasone following a CSDH. 750 patients were randomised to either dexamethasone or placebo. The primary outcome is the modi ed Rankin Scale at six months which is dichotomised to favourable (score of 0-3) versus unfavourable (score of 4-6). Conclusions: This paper and the accompanying additional material describes the statistical analysis plan for the trial.

Background Failure of cerebral autoregulation and progression of intracranial lesion have both been shown to contribute to poor outcome in patients with acute traumatic brain injury (TBI), but the interplay between the two phenomena has not been investigated. Preliminary evidence leads us to hypothesize that brain tissue adjacent to primary injury foci may be more vulnerable to large fluctuations in blood flow in the absence of intact autoregulatory mechanisms. The goal of this study was therefore to assess the influence of cerebrovascular reactivity measures on radiological lesion expansion in a cohort of patients with acute TBI. Methods We conducted a retrospective cohort analysis on 50 TBI patients who had undergone high-frequency multimodal intracranial monitoring and for which at least two brain computed tomography (CT) scans had been performed in the acute phase of injury. We first performed univariate analyses on the full cohort to identify non-neurophysiological factors (i.e., initial lesion volume, timing of scan, coagulopathy) associated with traumatic lesion growth in this population. In a subset analysis of 23 patients who had intracranial recording data covering the period between the initial and repeat CT scan, we then correlated changes in serial volumetric lesion measurements with cerebrovascular reactivity metrics derived from the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC (correlation coefficient between the pulse amplitude of intracranial pressure and cerebral perfusion pressure). Using multivariate methods, these results were subsequently adjusted for the non-neurophysiological confounders identified in the univariate analyses. Results We observed significant positive linear associations between the degree of cerebrovascular reactivity impairment and progression of pericontusional edema. The strongest correlations were observed between edema progression and the following indices of cerebrovascular reactivity between sequential scans: % time PRx > 0.25 (r = 0.69, p = 0.002) and % time PAx > 0.25 (r = 0.64, p = 0.006). These associations remained significant after adjusting for initial lesion volume and mean cerebral perfusion pressure. In contrast, progression of the hemorrhagic core and extra-axial hemorrhage volume did not appear to be strongly influenced by autoregulatory status. Conclusions Our preliminary findings suggest a possible link between autoregulatory failure and traumatic edema progression, which warrants re-evaluation in larger-scale prospective studies.

Funder: Evelyn Trust; funder-id: http://dx.doi.org/10.13039/501100004282, Funder: Raymond and Beverly Sackler Foundation; funder-id: http://dx.doi.org/10.13039/100013112, Traumatic brain injury (TBI) is a major cause of death and disability, particularly amongst young people. Current intensive care management of TBI patients is targeted at maintaining normal brain physiology and preventing secondary injury. Microdialysis is an invasive monitor that permits real-time assessment of derangements in cerebral metabolism and responses to treatment. We examined the prognostic value of microdialysis parameters, and the inter-relationships with other neuromonitoring modalities to identify interventions that improve metabolism. This was an analysis of prospective data in 619 adult TBI patients requiring intensive care treatment and invasive neuromonitoring at a tertiary UK neurosciences unit. Patients had continuous measurement of intracranial pressure (ICP), arterial blood pressure (ABP), brain tissue oxygenation (PbtO2), and cerebral metabolism and were managed according to a standardized therapeutic protocol. Microdialysate was assayed hourly for metabolites including glucose, pyruvate, and lactate. Cerebral perfusion pressure (CPP) and cerebral autoregulation (PRx) were derived from the ICP and ABP. Outcome was assessed with the Glasgow Outcome Score (GOS) at 6 months. Relationships between monitoring variables was examined with generalized additive mixed models (GAMM). Lactate/Pyruvate Ratio (LPR) over the first 3 to 7 days following injury was elevated amongst patients with poor outcome and was an independent predictor of ordinal GOS (p70mmHg, PRx 18mmHg, and brain glucose >1mM. Deranged cerebral metabolism is an important determinant of patient outcome following TBI. Variations in cerebral perfusion, oxygenation and glucose supply are associated with changes in cerebral LPR and suggest therapeutic interventions to improve cerebral metabolism. Future prospective studies are required to determine the efficacy of these strategies.

OBJECTIVES: To explore the frequency and nature of complaints and compliments reported to Patient Advice and Liaison (PALS) in individuals undergoing surgery for a chronic subdural haematoma (cSDH). DESIGN: A retrospective study of PALS user interactions. SUBJECTS: Individuals undergoing treatment for cSDH between 2014 and 2019. METHODS: PALS referrals from patients with cSDH between 2014 and 2019 were identified. Case records were reviewed and data on the frequency, nature and factors leading up to the complaint were extracted and coded according to Healthcare Complaints Analysis Tool (HCAT). RESULTS: Out of 531 patients identified, 25 (5%) had a PALS interaction, of which 15 (3%) were complaints and 10 (2%) were compliments. HCAT coding showed 8/15 (53%) of complaints were relationship problems, 6/15 (33%) a management problem and 1/15 (7%) other. Of the relationship problems, 6 (75%) were classed as problems with communication and 2 (25%) as a problem with listening. Of the compliments, 9/10 (90%) related to good clinical quality and 1/10 (10%) to staff-patient relationship. Patients were more likely to register a compliment than family members, who in turn were more likely to register a complaint (p, NIHR Clinical Doctoral Research Fellowship

Traumatic brain injury remains prevalent in children, particularly within the adolescent age group. In severe injury, the priority of treatment is to stabilise the patient initially and prevent the evolution of brain swelling and secondary ischaemia using tiers of medical therapy. The final stage of intervention for such patients is a decompressive craniectomy. Here in, we identify the current evidence for performing decompressive crainectomy in children including the results from the RESCUEicp study.

Impaired cerebrovascular reactivity in adult moderate and severe traumatic brain injury (TBI) is known to be associated with worse global outcome at 6-12 months. As technology has improved over the past decades, monitoring of cerebrovascular reactivity has shifted from intermittent measures, to experimentally validated continuously updating indices at the bedside. Such advances have led to the exploration of individualised physiologic targets in adult TBI management, such as optimal cerebral perfusion pressure (CPP) values, or CPP limits in which vascular reactivity is relatively intact. These targets have been shown to have a stronger association with outcome compared with existing consensus-based guideline thresholds in severe TBI care. This has sparked ongoing prospective trials of such personalised medicine approaches in adult TBI. In this narrative review paper, we focus on the concept of cerebral autoregulation, proposed mechanisms of control and methods of continuous monitoring used in TBI. We highlight multimodal cranial monitoring approaches for continuous cerebrovascular reactivity assessment, physiologic and neuroimaging correlates, and associations with outcome. Finally, we explore the recent 'state-of-the-art' advances in personalised physiologic targets based on continuous cerebrovascular reactivity monitoring, their benefits, and implications for future avenues of research in TBI.

Neurotrauma is an important global health problem. The largest cause of neurotrauma worldwide is road traffic collisions (RTCs), particularly in low- and middle-income countries (LMICs). Neurotrauma and RTCs are preventable, and many preventative interventions have been implemented over the last decades, especially in high-income countries (HICs). However, it is uncertain if these strategies are applicable globally due to variations in environment, resources, population, culture and infrastructure. Given this issue, this scoping review aims to identify, quantify and describe the evidence on approaches in neurotrauma and RTCs prevention, and ascertain contextual factors that influence their implementation in LMICs and HICs. A systematic search was conducted using five electronic databases (MEDLINE, EMBASE, CINAHL, Global Health on EBSCO host, Cochrane Database of Systematic Reviews), grey literature databases, government and non-government websites, as well as bibliographic and citation searching of selected articles. The extracted data were presented using figures, tables, and accompanying narrative summaries. The results of this review were reported using the PRISMA Extension for Scoping Reviews (PRISMA-ScR). A total of 411 publications met the inclusion criteria, including 349 primary studies and 62 reviews. More than 80% of the primary studies were from HICs and described all levels of neurotrauma prevention. Only 65 papers came from LMICs, which mostly described primary prevention, focussing on road safety. For the reviews, 41 papers (66.1%) reviewed primary, 18 tertiary (29.1%), and three secondary preventative approaches. Most of the primary papers in the reviews came from HICs (67.7%) with 5 reviews on only LMIC papers. Fifteen reviews (24.1%) included papers from both HICs and LMICs. Intervention settings ranged from nationwide to community-based but were not reported in 44 papers (10.8%), most of which were reviews. Contextual factors were described in 62 papers and varied depending on the interventions. There is a large quantity of global evidence on strategies and interventions for neurotrauma and RTCs prevention. However, fewer papers were from LMICs, especially on secondary and tertiary prevention. More primary research needs to be done in these countries to determine what strategies and interventions exist and the applicability of HIC interventions in LMICs.

BACKGROUND: Severe traumatic brain injury (TBI) is a leading cause of mortality in children, but the accurate prediction of outcomes at the point of admission remains very challenging. Admission laboratory results are a promising potential source of prognostic data, but have not been widely explored in paediatric cohorts. Herein, we use machine-learning methods to analyse 14 different serum parameters together and develop a prognostic model to predict 6-month outcomes in children with severe TBI. METHODS: A retrospective review of patients admitted to Cambridge University Hospital's Paediatric Intensive Care Unit between 2009 and 2013 with a TBI. The data for 14 admission serum parameters were recorded. Logistic regression and a support vector machine (SVM) were trained with these data against dichotimised outcomes from the recorded 6-month Glasgow Outcome Scale. RESULTS: Ninety-four patients were identified. Admission levels of lactate, H+, and glucose were identified as being the most informative of 6-month outcomes. Four different models were produced. The SVM using just the three most informative parameters was the best able to predict favourable outcomes at 6 months (sensitivity = 80%, specificity = 99%). CONCLUSIONS: Our results demonstrate the potential for highly accurate outcome prediction after severe paediatric TBI using admission laboratory data.

BACKGROUND: Drain insertion following chronic subdural hematoma (CSDH) evacuation improves patient outcomes. OBJECTIVE: To examine whether this is influenced by variation in drain location, positioning or duration of placement. METHODS: We performed a subgroup analysis of a previously reported multicenter, prospective cohort study of CSDH patients performed between May 2013 and January 2014. Data were analyzed relating drain location (subdural or subgaleal), position (through a frontal or parietal burr hole), and duration of insertion, to outcomes in patients aged >16 yr undergoing burr-hole drainage of primary CSDH. Primary outcomes comprised modified Rankin scale (mRS) at discharge and symptomatic recurrence requiring redrainage within 60 d. RESULTS: A total of 577 patients were analyzed. The recurrence rate of 6.7% (12/160) in the frontal subdural drain group was comparable to 8.8% (30/343) in the parietal subdural drain group. Only 44/577 (7.6%) patients underwent subgaleal drain insertion. Recurrence rates were comparable between subdural (7.7%; 41/533) and subgaleal (9.1%; 4/44) groups (P = .95). We found no significant differences in discharge mRS between these groups. Recurrence rates were comparable between patients with postoperative drainage for 1 or 2 d, 6.4% and 8.4%, respectively (P = .44). There was no significant difference in mRS scores between these 2 groups (P = .56). CONCLUSION: Drain insertion after CSDH drainage is important, but position (subgaleal or subdural) and duration did not appear to influence recurrence rate or clinical outcomes. Similarly, drain location did not influence recurrence rate nor outcomes where both parietal and frontal burr holes were made. Further prospective cohort studies or randomized controlled trials could provide further clarification.

OBJECTIVES: The detection of increasing intracranial pressure (ICP) is important in preventing secondary brain injuries. Before mean ICP increases critically, transient ICP elevations may be observed. We have observed ICP transients of less than 10 min duration ,which occurred simultaneously with transient increases in heart rate (HR). These simultaneous events in HR and ICP suggest a direct interaction or communication between the heart and the brain. METHODS: This chapter describes four mathematical methods and their applicability in detecting the above heart-brain cross-talk events during long-term monitoring of ICP. RESULTS: Recurrence plots, cross-correlation function and wavelet analysis confirmed the relationship between ICP and HR time series. Using the peaks detection algorithm with a sliding window approach we found an average of 37 cross-talk events (± SD 39). The number of events detected varied among patients, from 1 to more than 150 events. CONCLUSION: Our analysis suggested that the peaks detection algorithm based on a sliding window approach is feasible for detecting simultaneous peaks, e.g. cross-talk events in the ICP and HR signals.

The purpose of this study was to correlate the early levels of glial fibrillary acidic protein (GFAP) and neurofilament light protein (NF-L) with outcome in patients with mild traumatic brain injury (mTBI). A total of 107 patients with mTBI (Glasgow Coma Scale ≥13) who had blood samples for GFAP and NF-L available within 24 h of arrival were included. Patients with mTBI were divided into computed tomography (CT)-positive and CT-negative groups. Glasgow Outcome Scale-Extended (GOSE) was used to assess the outcome. Outcomes were defined as complete (GOSE 8) versus incomplete (GOSE

Background Chronic subdural haematoma (CSDH) is a common neurosurgical condition, typically treated with surgical drainage of the haematoma. However, surgery is associated with mortality and morbidity, including up to 20% recurrence of the CSDH. Steroids, such as dexamethasone, have been identified as a potential therapy for reducing recurrence risk in surgically treated CSDHs. They have also been used as a conservative treatment option, thereby avoiding surgery altogether. The hypothesis of the Dex-CSDH trial is that a two-week course of dexamethasone in symptomatic patients with CSDH will lead to better functional outcome at six months. This is anticipated to occur through reduced number of hospital admissions and surgical interventions. Methods Dex-CSDH is a UK multi-centre, double-blind randomised controlled trial of dexamethasone versus placebo for symptomatic adult patients diagnosed with CSDH. A sample size of 750 patients has been determined, including an initial internal pilot phase of 100 patients to confirm recruitment feasibility. Patients must be recruited within 72 h of admission to a neurosurgical unit and exclusions include patients already on steroids or with steroid contraindications, patients who have a cerebrospinal fluid shunt and those with a history of psychosis. The decision regarding surgical intervention will be made by the clinical team and patients can be included in the trial regardless of whether operative treatment is planned or has been performed. The primary outcome measure is the modified Rankin Scale (mRS) at six months. Secondary outcomes include the number of CSDH-related surgical interventions during follow-up, length of hospital stay, mRS at three months, EQ-5D at three and six months, adverse events, mortality and a health-economic analysis. Discussion This multi-centre trial will provide high-quality evidence as to the effectiveness of dexamethasone in the treatment of CSDH. This has implications for patient morbidity and mortality as well as a potential economic impact on the overall health service burden from this condition. Trial registration ISRCTN, ISRCTN80782810. Registered on 7 November 2014. EudraCT, 2014-004948-35. Registered on 20 March 2015. Dex-CSDH trial protocol version 3, 27 Apr 2017. This protocol was developed in accordance with the SPIRIT checklist. Available as a separate document on request. Electronic supplementary material The online version of this article (10.1186/s13063-018-3050-4) contains supplementary material, which is available to authorized users.

BACKGROUND: Public engagement has become one of the most effective tools in gaining feedback and perspectives from members of the public, involving patients with decisions, and inspiring young people to carry the medical profession forwards. Brainbook is a multi-platform, social media-based resource that was created specifically to enhance public engagement in neurosurgery and results from one of its case discussions will be reported in this paper. METHODS: A Brainbook case was created in collaboration with the NIHR Global Health Research Group on Neurotrauma and presented over 3 days (23-25 February 2018). YouTube videos were created depicting the management of an acute subdural haematoma using patient interviews, medical illustration, consultant-led discussion and operative footage. Content was shared across all Brainbook social media platforms and analytics were gathered through social media applications. RESULTS: Over a 72-hour time period, and across multiple social media accounts, 101,418 impressions were achieved (defined as penetrance onto individual media feeds and total views of the content), with active discussion on social media. CONCLUSIONS: Neurosurgical content published across multiple social media outlets represents an encouraging and exciting potential for global engagement across multiple audiences. Social media can be an effective method of not only disseminating neurosurgical knowledge, but activating and engaging the public, allied healthcare professionals, medical students and neurosurgeons.

Cortical spreading depolarization (CSD) is an emerging mode of secondary neuronal damage in acute brain injury (ABI). Subsequent repolarisation is a metabolic process requiring glucose. Instances of CSD and glucose derangement are both linked to poor neurological outcome, but their causal inter-relationship is not fully defined. This systematic review seeks to evaluate the available human evidence studying CSD and glucose to further understand their dynamic relationship. We conducted a systematic review of studies examining CSD through electrocorticography and cerebral/systemic glucose concentrations in ABI, excluding animal studies. The search yielded 478 articles, of which 13 were eligible. Across 10 manuscripts, 125 patients received simultaneous monitoring, with 1987 CSD episodes observed. Eight of 10 studies observed correlation between CSD and glucose change. Seven of eight studies observed possible cumulative effect of recurrent CSD on glucose derangement and two identified correlation between glycopenia and incidence of CSD. These findings confirm a relationship between CSD and glucose, and suggest it may be cyclical, where CSD causes local glycopenia, which may potentiate further CSD. Positive observations were not common to all studies, likely due to differing methodology or heterogeneity in CSD propensity. Further study is required to delineate the utility of the clinical modulation of serum and cerebral glucose to alter the propensity for CSD following brain injury.

The purpose of this study was to correlate the early levels of glial fibrillary acidic protein (GFAP) and neurofilament light protein (NF-L) with outcome in patients with mild traumatic brain injury (mTBI). 107 patients with mTBI [Glasgow Coma Scale (GCS) ≥13] having the blood samples for GFAP and NF-L available within 24 hrs from arrival were included. Patients with mTBI were divided into computed tomography (CT)-positive and CT-negative groups. Glasgow Outcome Scale extended (GOSE) was used to assess the outcome. Outcomes were defined as complete (GOSE 8) vs. incomplete (GOSE, This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), Integra EANS Research Grant (IH), University of Turku Graduate School funding (MM), Government’s Special Financial Transfer tied to academic research in Health Sciences (JPP, RSKT), and personal grants from Emil Aaltonen Foundation sr and Finnish Brain Foundation sr (JPP)

Cerebral autoregulatory dysfunction after traumatic brain injury (TBI) is strongly linked to poor global outcome in patients at 6 months after injury. However, our understanding of what drives this dysfunction is limited. Genetic variation among individuals within a population gives rise to single nucleotide polymorphisms (SNPs) that have the potential to influence a given patient’s cerebrovascular response to an injury. Associations have been reported between a variety of genetic polymorphisms and global outcome in patients with TBI, but few studies have explored the association between genetics and cerebrovascular function after injury. In this Review, we explore polymorphisms that might play an important part in cerebral autoregulatory capacity after TBI. We outline a variety of SNPs, their biological substrates and their potential role in mediating cerebrovascular reactivity. A number of candidate polymorphisms exist in genes that are involved in myogenic, endothelial, metabolic and neurogenic vascular responses to injury. Furthermore, polymorphisms in genes involved in inflammation, the central autonomic response and spreading cortical depression might drive cerebrovascular reactivity. Identification of candidate genes involved in cerebral autoregulation after TBI provides a platform and rationale for further prospective investigation of the link between genetic polymorphisms and autoregulatory function.

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.

Background: Patients with traumatic brain injury (TBI) exhibit a variable and unpredictable outcome. The proteins interleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have shown predictive values for the presence of intracranial lesions. Aim: To evaluate the individual and combined outcome prediction ability of IL-10 and H-FABP, and to compare them to the more studied proteins S100β, glial fibrillary acidic protein (GFAP), and neurofilament light (NF-L), both with and without clinical predictors. Methods: Blood samples from patients with acute TBI (all severities) were collected 6 months post injury using the Glasgow Outcome Scale Extended (GOSE) score, dichotomizing patients into: (i) those with favorable (GOSE≥5)/unfavorable outcome (GOSE ≤ 4) and complete (GOSE = 8)/incomplete (GOSE ≤ 7) recovery, and (ii) patients with mild TBI (mTBI) and patients with TBIs of all severities. Results: When sensitivity was set at 95–100%, the proteins' individual specificities remained low. H-FABP showed the best specificity (%) and sensitivity (100%) in predicting complete recovery in patients with mTBI. IL-10 had the best specificity (50%) and sensitivity (96%) in identifying patients with favorable outcome in patients with TBIs of all severities. When individual proteins were combined with clinical parameters, a model including H-FABP, NF-L, and ISS yielded a specificity of 56% and a sensitivity of 96% in predicting complete recovery in patients with mTBI. In predicting favorable outcome, a model consisting IL-10, age, and TBI severity reached a specificity of 80% and a sensitivity of 96% in patients with TBIs of all severities. Conclusion: Combining novel TBI biomarkers H-FABP and IL-10 with GFAP, NF-L and S100β and clinical parameters improves outcome prediction models in TBI.

BACKGROUND: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) are promising biomarkers of traumatic brain injury (TBI). OBJECTIVE: We investigated the relation of the GFAP and UCH-L1 levels to the severity of TBI during the first week after injury. METHODS: Plasma UCH-L1 and GFAP were measured from 324 consecutive patients with acute TBI and 81 control subject enrolled in a 2-center prospective study. The baseline measures included initial Glasgow Coma Scale (GCS), head computed tomographic (CT) scan at admission, and blood samples for protein biomarkers that were collected at admission and on days 1, 2, 3, and 7 after injury. RESULTS: Plasma levels of GFAP and UCH-L1 during the first 2 days after the injury strongly correlated with the initial severity of TBI as assessed with GCS. Additionally, levels of UCH-L1 on the seventh day after the injury were significantly related to the admission GCS scores. At admission, both biomarkers were capable of distinguishing mass lesions from diffuse injuries in CT, and the area under the curve of the receiver-operating characteristic curve for prediction of any pathological finding in CT was 0.739 (95% confidence interval, 0.636-0.815) and 0.621 (95% confidence interval, 0.517-0.713) for GFAP and UCH-L1, respectively. CONCLUSION: These results support the prior findings of the potential role of GFAP and UCH-L1 in acute-phase diagnostics of TBI. The novel finding is that levels of GFAP and UCH-L1 correlated with the initial severity of TBI during the first 2 days after the injury, thus enabling a window for TBI diagnostics with latency. ABBREVIATIONS: AUC, area under the curveCI, confidence intervalED, emergency departmentGCS, Glasgow Coma ScaleGRAP, glial fibrillary acidic proteinIMPACT, International Mission for Prognosis and Clinical TrialROC, receiver-operating characteristicTBI, traumatic brain injuryTRACK-TBI, Transforming Research and Clinical Knowledge in Traumatic Brain InjuryUCH-L1, ubiquitin C-terminal hydrolase-L1.

The plethora of studies in chronic subdural hematoma (CSDH) has not resulted in the development of an evidence-based treatment strategy, largely due to heterogeneous outcome measures that preclude cross-study comparisons and guideline development. This study aimed to identify and quantify the heterogeneity of outcome measures reported in the CSDH literature and to build a case for the development of a consensus-based core outcome set. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered with the PROSPERO international prospective register of systematic reviews (CRD42014007266). All full-text English language studies with >10 patients (prospective) or >100 patients (retrospective) published after 1990 examining clinical outcomes in CSDH were eligible for inclusion. One hundred two eligible studies were found. There were 14 (13.7%) randomized controlled trials, one single arm trial (1.0%), 25 (24.5%) cohort comparison studies, and 62 (60.8%) prospective or retrospective cohort studies. Outcome domains reported by the studies included mortality (63.8% of included studies), recurrence (94.1%), complications (48.0%), functional outcomes (40.2%), and radiological (38.2%) outcomes. There was significant heterogeneity in the definitions of the outcome measures, as evidenced by the seven different definitions of the term “recurrence,” with no definition given in 19 studies. The time-points of assessment for all the outcome domains varied greatly from inpatient/hospital discharge to 18 months. This study establishes and quantifies the heterogeneity of outcome measure reporting in CSDH and builds the case for the development of a robust consensus-based core outcome set for future studies to adhere to as part of the Core Outcomes and Common Data Elements in CSDH (CODE-CSDH) project.

In the context of traumatic brain injury (TBI), decompressive craniectomy (DC) is used as part of tiered therapeutic protocols for patients with intracranial hypertension (secondary or protocol-driven DC). In addition, the bone flap can be left out when evacuating a mass lesion, usually an acute subdural haematoma (ASDH), in the acute phase (primary DC). Even though, the principle of “opening the skull” in order to control brain oedema and raised intracranial pressure has been practised since the beginning of the 20th century, the last 20 years have been marked by efforts to develop the evidence base with the conduct of randomised trials. This article discusses the merits and challenges of this approach and provides an overview of randomised trials of DC following TBI. An update on the RESCUEicp study, a randomised trial of DC versus advanced medical management (including barbiturates) for severe and refractory post-traumatic intracranial hypertension is provided. In addition, the rationale for the RESCUE-ASDH study, the first randomised trial of primary DC versus craniotomy for adult head-injured patients with an ASDH, is presented.

BACKGROUND: Intracranial pressure (ICP) is a clinically important variable after severe traumatic brain injury (TBI) and has been monitored, along with clinical outcome, for over 25 yr in Addenbrooke's hospital, Cambridge, United Kingdom. This time period has also seen changes in management strategies with the implementation of protocolled specialist neurocritical care, expansion of neuromonitoring techniques, and adjustments of clinical treatment targets. OBJECTIVE: To describe the changes in intracranial monitoring variables over the past 25 yr. METHODS: Data from 1146 TBI patients requiring ICP monitoring were analyzed. Monitored variables included ICP, cerebral perfusion pressure (CPP), and the cerebral pressure reactivity index (PRx). Data were stratified into 5-yr epochs spanning the 25 yr from 1992 to 2017. RESULTS: CPP increased sharply with specialist neurocritical care management (P < 0.0001) (introduction of a specific TBI management algorithm) before stabilizing from 2000 onwards. ICP decreased significantly over the 25 yr of monitoring from an average of 19 to 12 mmHg (P < 0.0001) but PRx remained unchanged. The mean number of ICP plateau waves and the number of patients developing refractory intracranial hypertension both decreased significantly. Mortality did not significantly change in the cohort (22%). CONCLUSION: We demonstrate the evolving trends in neurophysiological monitoring over the past 25 yr from a single, academic neurocritical care unit. ICP and CPP were responsive to the introduction of an ICP/CPP protocol while PRx has remained unchanged.

IntroductionLow-income and middle-income countries (LMICs) face the greatest burden of neurotrauma. However, most of the research published in scientific journals originates from high-income countries, suggesting those in LMICs are either not engaging in research or are not publishing it. Evidence originating in high-income countries may not be generalisable to LMICs; therefore, it is important to nurture research capacity in LMICs so that a relevant evidence base can be developed. However, little is published about specific challenges or contextual issues relevant to increasing research activity of neurosurgeons in LMICs. Therefore, the aim of this study was to understand neurosurgeons’ experiences of, aspirations for and ability to conduct and disseminate clinical research in LMICs.Methods and analysisThis is a pragmatic qualitative study situated within the naturalistic paradigm using focus groups and interviews with a purposive sample of neurosurgeons from LMICs. First, we will conduct asynchronous online focus groups with 36 neurosurgeons to broadly explore issues relevant to the study aim. Second, we will select 20 participants for follow-up semistructured interviews to explore concepts in more depth and detail than could be achieved in the focus group. Interviews will be audio-recorded and transcribed verbatim. A thematic analysis will be conducted following Braun and Clarke’s six stages and will be supported by NVIVO software.Ethics and disseminationThe University of Cambridge Psychology Research Ethics Committee reviewed this study and provided a favourable opinion in January 2020 (REF PRE.2020.006). Participants will provide informed consent, be able to withdraw at any time and will have their contributions kept confidential. The findings of the study will be shared with relevant stakeholders and disseminated in conference presentations and journal publications.