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Objective To estimate the cost-effectiveness of craniotomy, compared with decompressive craniectomy (DC) in UK patients undergoing evacuation of acute subdural haematoma (ASDH).Design Economic evaluation undertaken using health resource use and outcome data from the 12-month multicentre, pragmatic, parallel-group, randomised, Randomised Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation-ASDH trial.Setting UK secondary care.Participants 248 UK patients undergoing surgery for traumatic ASDH were randomised to craniotomy (N=126) or DC (N=122).Interventions Surgical evacuation via craniotomy (bone flap replaced) or DC (bone flap left out with a view to replace later: cranioplasty surgery).Main outcome measures In the base-case analysis, costs were estimated from a National Health Service and Personal Social Services perspective. Outcomes were assessed via the quality-adjusted life-years (QALY) derived from the EuroQoL 5-Dimension 5-Level questionnaire (cost-utility analysis) and the Extended Glasgow Outcome Scale (GOSE) (cost-effectiveness analysis). Multiple imputation and regression analyses were conducted to estimate the mean incremental cost and effect of craniotomy compared with DC. The most cost-effective option was selected, irrespective of the level of statistical significance as is argued by economists.Results In the cost-utility analysis, the mean incremental cost of craniotomy compared with DC was estimated to be −£5520 (95% CI −£18 060 to £7020) with a mean QALY gain of 0.093 (95% CI 0.029 to 0.156). In the cost-effectiveness analysis, the mean incremental cost was estimated to be −£4536 (95% CI −£17 374 to £8301) with an OR of 1.682 (95% CI 0.995 to 2.842) for a favourable outcome on the GOSE.Conclusions In a UK population with traumatic ASDH, craniotomy was estimated to be cost-effective compared with DC: craniotomy was estimated to have a lower mean cost, higher mean QALY gain and higher probability of a more favourable outcome on the GOSE (though not all estimated differences between the two approaches were statistically significant).Ethics Ethical approval for the trial was obtained from the North West—Haydock Research Ethics Committee in the UK on 17 July 2014 (14/NW/1076).Trial registration number ISRCTN87370545.

Background Chronic subdural haematoma is a collection of ‘old blood’ and its breakdown products in the subdural space and predominantly affects older people. Surgical evacuation remains the mainstay in the management of symptomatic cases. Objective The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) randomised trial investigated the clinical effectiveness and cost-effectiveness of dexamethasone in patients with a symptomatic chronic subdural haematoma. Design This was a parallel, superiority, multicentre, pragmatic, randomised controlled trial. Assigned treatment was administered in a double-blind fashion. Outcome assessors were also blinded to treatment allocation. Setting Neurosurgical units in the UK. Participants Eligible participants included adults (aged ≥ 18 years) admitted to a neurosurgical unit with a symptomatic chronic subdural haematoma confirmed on cranial imaging. Interventions Participants were randomly assigned in a 1 : 1 allocation to a 2-week tapering course of dexamethasone or placebo alongside standard care. Main outcome measures The primary outcome was the Modified Rankin Scale score at 6 months dichotomised to a favourable (score of 0–3) or an unfavourable (score of 4–6) outcome. Secondary outcomes included the Modified Rankin Scale score at discharge and 3 months; number of chronic subdural haematoma-related surgical interventions undertaken during the index and subsequent admissions; Barthel Index and EuroQol 5-Dimension 5-Level utility index score reported at discharge, 3 months and 6 months; Glasgow Coma Scale score reported at discharge and 6 months; mortality at 30 days and 6 months; length of stay; discharge destination; and adverse events. An economic evaluation was also undertaken, during which the net monetary benefit was estimated at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. Results A total of 748 patients were included after randomisation: 375 were assigned to dexamethasone and 373 were assigned to placebo. The mean age of the patients was 74 years and 94% underwent evacuation of their chronic subdural haematoma during the trial period. A total of 680 patients (91%) had 6-month primary outcome data available for analysis: 339 in the placebo arm and 341 in the dexamethasone arm. On a modified intention-to-treat analysis of the full study population, there was an absolute reduction in the proportion of favourable outcomes of 6.4% (95% confidence interval 11.4% to 1.4%; p = 0.01) in the dexamethasone arm compared with the control arm at 6 months. At 3 months, the between-group difference was also in favour of placebo (−8.2%, 95% confidence interval −13.3% to −3.1%). Serious adverse events occurred in 60 out of 375 (16.0%) in the dexamethasone arm and 24 out of 373 (6.4%) in the placebo arm. The net monetary benefit of dexamethasone compared with placebo was estimated to be –£97.19. Conclusions This trial reports a higher rate of unfavourable outcomes at 6 months, and a higher rate of serious adverse events, in the dexamethasone arm than in the placebo arm. Dexamethasone was also not estimated to be cost-effective. Therefore, dexamethasone cannot be recommended for the treatment of chronic subdural haematoma in this population group. Future work and limitations A total of 94% of individuals underwent surgery, meaning that this trial does not fully define the role of dexamethasone in conservatively managed haematomas, which is a potential area for future study. Trial registration This trial is registered as ISRCTN80782810. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/15/02) and is published in full in Health Technology Assessment; Vol. 28, No. 12. See the NIHR Funding and Awards website for further award information. Plain language summary Chronic subdural haematoma is one of the most common conditions managed in adult neurosurgery and mainly affects older people. It is an ‘old’ collection of blood and blood breakdown products found on the surface of the brain. Surgery to drain the liquid collection is effective, with most patients improving. Given that inflammation is involved in the disease process, a commonly used steroid, dexamethasone, has been used alongside surgery or instead of surgery since the 1970s. However, there is no consensus or high-quality studies confirming the effectiveness of dexamethasone for the treatment of chronic subdural haematoma. This study was designed to determine the effectiveness of adding dexamethasone to the normal treatment for patients with a symptomatic chronic subdural haematoma. The benefit of adding dexamethasone was measured using a disability score called the Modified Rankin Scale, which can be divided into favourable and unfavourable outcomes. This was assessed at 6 months after entry into the study. In total, 748 adults with a symptomatic chronic subdural haematoma treated in neurosurgical units in the UK participated. Each participant had an equal chance of receiving either dexamethasone or a placebo because they were assigned randomly. Neither the patients nor the investigators knew who received dexamethasone and who received placebo. Most patients in both groups had an operation to drain the haematoma and experienced significant functional improvement at 6 months compared with their initial admission to hospital. However, patients who received dexamethasone had a lower chance than patients who received placebo of favourable recovery at 6 months. Specifically, 84% of patients who received dexamethasone had recovered well at 6 months, compared with 90% of patients who received placebo. There were more complications in the group that received dexamethasone. This trial demonstrates that adding dexamethasone to standard treatment reduced the chance of a favourable outcome compared with standard treatment alone. Therefore, this study does not support the use of dexamethasone in treating patients with a symptomatic chronic subdural haematoma. Scientific summary Background Chronic subdural haematoma (CSDH) is a common neurological disorder predominantly affecting older people, affecting approximately 5000 people aged over 65 years in the UK each year. Its incidence is increasing owing to an ageing population, alongside the growing use of antithrombotic agents. The majority of CSDHs do not cause symptoms and are managed conservatively. In those that do cause symptoms, surgical evacuation remains the mainstay of management, which achieves a good recovery in approximately 80% of patients. The remaining 10–20% of patients may suffer a recurrence, requiring further surgery. Additional and alternative measures to surgery are sought to improve outcomes in this patient group. Inflammation has been implicated in the pathogenesis of CSDHs, which suggests a role for anti-inflammatory medications, such as steroids. Therefore, steroids may serve as a useful adjunct or even alternative to surgery. However, to date, there is a lack of high-quality evidence in the form of a randomised clinical trial or meta-analysis. This trial investigates the clinical effectiveness of a steroid, dexamethasone, in patients with symptomatic CSDH. Objectives Primary objective The primary objective of the trial was to determine the clinical effectiveness of a 2-week course of dexamethasone for adult patients with a symptomatic CSDH, assessed by comparing the rate of favourable outcomes [defined as a Modified Rankin Scale (mRS) score of 0–3] at 6 months after randomisation between the treatment and the control arm. This outcome was reviewed centrally by a clinically trained investigator blinded to treatment allocation. Secondary objectives The secondary objectives were to compare the following outcomes between the treatment and the control arm of the trial: number of CSDH-related surgical interventions undertaken during the index admission number of CSDH-related surgical interventions undertaken during subsequent admissions in the follow-up period Glasgow Coma Scale (GCS) score at discharge from the neurosurgical unit (NSU) and at 6 months Modified Rankin Scale score at discharge from the NSU and at 3 months Barthel Index score at discharge from the NSU and at 3 and 6 months mortality (30 days and 6 months) EuroQol-5 Dimensions, five-level version (EQ-5D-5L), utility index at discharge from the NSU and at 3 and 6 months length of stay in the NSU discharge destination from the NSU length of stay in secondary care rates of adverse events (AEs). An economic evaluation was also undertaken to estimate the cost-effectiveness of dexamethasone compared with placebo. Tertiary objectives Postoperative recurrence is a tertiary outcome measure and is defined as a symptomatic recurrence requiring reoperation of a previously evacuated ipsilateral CSDH. Methods Trial design The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) trial is a multicentre, pragmatic, clinical phase III, randomised, double-blind, placebo-controlled trial of a tapering 2-week course of dexamethasone in patients with a symptomatic CSDH. The pragmatic design meant that the trial ran in parallel with standard clinical care, with the only difference being the addition of the trial drug (dexamethasone) or placebo. Intervention Two-week tapering course of dexamethasone (with matching placebo as the control). Participants Participants were screened for eligibility from 23 NSUs across the UK, with the admitting neurosurgical team determining eligibility for participation. Participants were adult patients aged ≥ 18 years with a symptomatic CSDH confirmed on cranial imaging (computerised tomography or magnetic resonance imaging of the brain). The patient or their legal representative had to provide informed consent. In the absence of a legal representative, an independent healthcare professional provided authorisation for enrolment. Patients were excluded in the presence of any of the following criteria: presence of a condition for which steroids are clearly contraindicated patients who are (or within 1 month of) receiving regular oral or intravenous glucocorticoid steroids (this did not include inhaled or topical steroids, nor did it include those receiving a single intraoperative dose of dexamethasone for anti-emesis) previous enrolment in this trial for a prior episode time interval from time of admission to the NSU to first dose of trial medication exceeded 72 hours chronic subdural haematoma in the presence of a cerebrospinal fluid shunt severe lactose intolerance or a known hypersensitivity to dexamethasone or other excipients a history of psychotic disorders unwillingness to take products containing gelatine. Patients who were screened but not included in the study were recorded on a screening log and reported centrally, with both the number of failures and the reasons for failure to recruit to the trial documented. Trial procedures Patients were managed in NSUs in accordance with standard practice. In the UK, this typically includes burr hole evacuation with the use of a subdural drain for most symptomatic patients. The decision for surgery or active monitoring was made on an individual patient basis by the blinded admitting clinical team in conjunction with the patient, in keeping with the pragmatic nature of the trial. Enrolment in the trial took place irrespective of the decision to operate and the timing of surgical intervention. Patients were randomised in 1 : 1 allocation using a computer-generated randomisation schedule, stratified by site using permuted blocks of random sizes (two or four). An interactive web-based response system was used to allocate treatment packs of 62 overencapsulated 2-mg dexamethasone tablets or 62 identical placebo capsules. The enrolled participants, clinical and research team and outcome assessors were blinded to the treatment allocation. The assigned treatment was administered as part of the routine drug round by the ward nurses. Oral administration was the preferred option, but administration via a nasogastric tube was offered to those unable to swallow. The latter method required opening of the capsules for crushing of the contents, allowing potential unblinding of the ward nurse. Therefore, the content of any opened capsules was not documented in the patient notes to maintain the blinding of the neurosurgeons and research staff. Trial drug compliance was recorded through inpatient drug charts during admission or by completion of a medication diary. Data were collected at baseline (on admission to the neurosurgical department) as part of routine standard of care, on discharge from the acute NSU, at 30 days, at 3 months and at 6 months. Patients were monitored in line with routine clinical practice until discharge, and at 3 and 6 months, to score clinical outcomes. Sample size This sample size was calculated with the following assumptions: a favourable outcome rate of 80–85% in the control arm and allowing for up to 15% loss to follow-up. A target sample size of 750 patients was needed to detect an increase in favourable outcome rate from 80–85% to 88–93%, with a power of 81–92% at the 5% significance level (two sided). An 8% increase in the rate of favourable outcome (mRS score of 0–3) at 6 months represents a clinically important treatment effect. Statistical analysis Data were analysed in accordance with the prespecified statistical analysis plan that was agreed prior to unblinding of data. Outcome data were analysed using a modified intention-to-treat analysis (all patients were included as randomised, except for those who withdrew consent for participation in the trial and those lost to follow-up). The primary outcome (mRS score at 6 months) was dichotomised into favourable (0–3) or unfavourable (4–6) outcomes. Primary analysis estimated the absolute difference between the intervention arm and the control arm in the proportions achieving a favourable outcome. A normal approximation was used to produce 95% confidence intervals (CIs) and a two-sided p-value testing the null hypothesis of no difference. Secondary analysis included a logistic regression and proportional odds logistic regression of the original mRS score adjusting for baseline covariates of age and Glasgow Coma Scale (GCS) score. Economic evaluation In the base-case analysis, costs were estimated over the 6-month trial period from an NHS and a Personal Social Services perspective. Outcomes were quality-adjusted life-years (QALYs) derived from the EuroQol-5 Dimensions, five-level version (EQ-5D-5L), at NSU discharge and at the 3- and 6-month follow-ups. Analyses were undertaken to estimate the mean incremental cost and effect, and enable the net monetary benefit (NMB) (a negative score indicates that the intervention is not estimated to be cost-effective) to be calculated, along with the cost-effectiveness acceptability curve (CEAC) (probability that dexamethasone was cost-effective). NMB and CEAC values at a willingness-to-pay threshold of £20,000 per QALY are reported. Results Primary outcome An outcome of mRS score of 0–3 occurred in 286 out of 341 patients (83.9%) in the dexamethasone arm and 306 out of 339 patients (90.3%) in the placebo arm at 6 months (difference −6.4%, 95% CI −11.4% to −1.4%; p = 0.01). After adjustment for prespecified covariates (age > 70 years and GCS score on admission), the odds ratio (OR) of a favourable outcome with dexamethasone was 0.55 (95% CI 0.33 to 0.91; p = 0.022), favouring placebo. Secondary outcomes Modified Rankin Scale at discharge and 3 months At 3 months, 268 out of 322 patients (83.2%) in the dexamethasone arm and 298 out of 326 patients (91.4%) in the placebo arm had a favourable outcome, for a between-group difference of −8.2% (95% CI −13.3% to −3.1%) in favour of the placebo arm. There was no significant difference in mRS score between the two arms at discharge [255/318 (80.2%) in the dexamethasone arm and 263/316 (83.2%) in the placebo arm for a difference of −3.0% (95% CI −9.1% to 3.0%)]. Mortality At discharge, 8 out of 375 patients (2.1%) in the dexamethasone arm and 2 out of 373 patients (0.5%) in the placebo arm had died (OR 4.08, 95% CI 1.01 to 27.2). At 6 months, 30 out of 341 patients (8.8%) in the dexamethasone arm and 17 out of 339 patients (5.0%) in the placebo arm had died (OR 1.83, 95% CI 0.99 to 3.45). Number of chronic subdural haematoma-related surgical interventions undertaken The number of surgical interventions undertaken during the index admission or during subsequent admissions during the follow-up period was similar in both arms. However, in the subset of patients who received surgery, repeat surgery for recurrence of the CSDH was performed in 6 out of 349 patients (1.7%) in the dexamethasone arm and in 25 out of 350 patients (7.1%) in the placebo arm. EuroQol-5 Dimensions, five-level version, utility index (at discharge and at 3 and 6 months) The mean EQ-5D-5L, utility index scores were compared. At discharge, the difference was −0.03 (95% CI −0.07 to 0.01), favouring placebo. At 3 months, the difference was −0.07 (95% CI −0.12 to −0.02), favouring placebo. At 6 months, the difference was −0.03 (95% CI −0.09 to 0.02), favouring placebo. Glasgow Coma Scale (at discharge and at 6 months) Glasgow Coma Scale was grouped into scores of 9–12 and 13–15. The percentage of patients with a score of 13–15 was similar at discharge (99.7% in the placebo arm vs. 99.2% in the dexamethasone arm). Insufficient data at 6 months prevented analysis. Barthel Index (at discharge and at 3 and 6 months) No significant difference was seen between the placebo arm and the dexamethasone arm at discharge, 3 months or 6 months. Length of stay in the neurosurgical unit The mean length of stay was 9.03 days in the placebo arm and 9.32 days in the dexamethasone arm. Length of stay in secondary care The mean length of stay was 13.0 days in the dexamethasone arm and 13.7 days in the placebo arm, with no significant difference between the two arms (0.95, 95% CI 0.835 to 1.09; p = 0.467). Discharge destination from the neurosurgical unit No significant difference was observed between the placebo arm and the dexamethasone arm when comparing discharge destinations. Rates of adverse events The odds of an adverse event of special interest were greater in the dexamethasone arm than in the placebo arm (OR 3.40, 95% CI 1.81 to 6.85). Similarly, the odds of a serious adverse event occurring were greater in the dexamethasone arm than in the placebo arm (OR 2.49, 95% CI 1.54 to 4.15). Economic evaluation The mean incremental cost for dexamethasone was estimated to be −£143.73 (95% CI −£1793 to £1505), with a QALY of −0.012 (95% CI −0.027 to 0.003), compared with placebo. The associated NMB of dexamethasone compared with placebo was −£97.19, with an estimated 46% probability of being cost-effective. Conclusions Implications for healthcare Dexamethasone for the treatment of symptomatic CSDH resulted in a lower proportion of favourable outcomes, as measured with the mRS, and a larger number of AEs than placebo. This treatment regime was also not estimated to be cost-effective (based on the NMB). Therefore, dexamethasone is not recommended in the treatment of CSDH. Implications for research The results of our literature review indicate that this study is the first multicentre randomised controlled trial to investigate the clinical effectiveness and cost-effectiveness of dexamethasone in the management of symptomatic CSDH. It provides evidence to inform the role of dexamethasone in this condition. Trial registration This trial is registered as ISRCTN80782810. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/15/02) and is published in full in Health Technology Assessment; Vol. 28, No. 12. See the NIHR Funding and Awards website for further award information.

Introduction: A common neurosurgical condition, chronic subdural haematoma (cSDH) typically affects older people with other underlying health conditions. The care of this potentially vulnerable cohort is often, however, fragmented and suboptimal. In other complex conditions, multidisciplinary guidelines have transformed patient experience and outcomes, but no such framework exists for cSDH. This paper outlines a protocol to develop the first comprehensive multidisciplinary guideline from diagnosis to long-term recovery with cSDH. Methods: The project will be guided by a steering group of key stakeholders and professional organisations and will feature patient and public involvement. Multidisciplinary thematic working groups will examine key aspects of care to formulate appropriate, patient-centered research questions, targeted with evidence review using the GRADE framework. The working groups will then formulate draft clinical recommendations to be used in a modified Delphi process to build consensus on guideline contents. Conclusions: We present a protocol for the development of a multidisciplinary guideline to inform the care of patients with a cSDH, developed by cross-disciplinary working groups and arrived at through a consensus-building process, including a modified online Delphi.

BackgroundCerebrospinal fluid rhinorrhoea (CSFR) is a common complication following endonasal skull base surgery, a technique that is fundamental to the treatment of pituitary adenomas and many other skull base tumours. The CRANIAL study explored CSFR incidence and related risk factors, particularly skull base repair techniques, via a multicentre prospective observational study. We sought to use machine learning to leverage this complex multicentre dataset for CSFR prediction and risk factor analysis.MethodsA dataset of 865 cases - 725 transsphenoidal approach (TSA) and 140 expanded endonasal approach (EEA) - with cerebrospinal fluid rhinorrhoea as the primary outcome, was used. Relevant variables were extracted from the data, and prediction variables were divided into two categories, preoperative risk factors; and repair techniques, with 6 and 11 variables respectively. Three types of machine learning models were developed in order to predict CSFR: logistic regression (LR); decision tree (DT); and neural network (NN). Models were validated using 5-fold cross-validation, compared via their area under the curve (AUC) evaluation metric, and key prediction variables were identified using their Shapley additive explanations (SHAP) score.ResultsCSFR rates were 3.9% (28/725) for the transsphenoidal approach and 7.1% (10/140) for the expanded endonasal approach. NNs outperformed LR and DT for CSFR prediction, with a mean AUC of 0.80 (0.70-0.90) for TSA and 0.78 (0.60-0.96) for EEA, when all risk factor and intraoperative repair data were integrated into the model. The presence of intraoperative CSF leak was the most prominent risk factor for CSFR. Elevated BMI and revision surgery were also associated with CSFR for the transsphenoidal approach. CSF diversion and gasket sealing appear to be strong predictors of the absence of CSFR for both approaches.ConclusionNeural networks are effective at predicting CSFR and uncovering key CSFR predictors in patients following endonasal skull base surgery, outperforming traditional statistical methods. These models will be improved further with larger and more granular datasets, improved NN architecture, and external validation. In the future, such predictive models could be used to assist surgical decision-making and support more individualised patient counselling.

BackgroundChronic subdural haematoma (CSDH) is becoming increasingly prevalent, due to an aging population with increasing risk factors. Due to its variable disease course and high morbidity, patient centred care and shared decision making are essential. However, its occurrence in frail populations, remote from specialist neurosurgeons who currently triage treatment decisions, challenges this. Education is an important component of enabling shared decisions. This should be targeted to avoid information overload. However, it is unknown what this should be.ObjectivesOur objectives were to conduct analysis of the content of existing CSDH educational materials, to inform the development of patient and relative educational resources to facilitate shared decision making.MethodsA literature search was conducted (July 2021) of MEDLINE, Embase and grey literature, for all self-specified resources on CSDH education, and narrative reviews. Resources were classified into a hierarchical framework using inductive thematic analysis into 8 core domains: Aetiology, epidemiology and pathophysiology; natural history and risk factors; symptoms; diagnosis; surgical management; nonsurgical management; complications and recurrence; and outcomes. Domain provision was summarised using descriptive statistics and Chi-squared tests.Results56 information resources were identified. 30 (54%) were resources designed for healthcare professionals (HCPs), and 26 (46%) were patient-orientated resources. 45 (80%) were specific to CSDH, 11 (20%) covered head injury, and 10 (18%) referenced both acute and chronic SDH. Of 8 core domains, the most reported were aetiology, epidemiology and pathophysiology (80%, n = 45) and surgical management (77%, n = 43). Patient orientated resources were more likely to provide information on symptoms (73% vs 13%, pConclusionThe content of educational resources is varied, even amongst those intended for the same audience. These discrepancies indicate an uncertain educational need, that will need to be resolved in order to better support effective shared decision making. The taxonomy created can inform future qualitative studies.

ObjectiveDespite progress in endonasal skull-base neurosurgery, cerebrospinal fluid (CSF) rhinorrhoea remains common and significant. The CRANIAL study sought to determine 1) the scope of skull-base repair methods used, and 2) corresponding rates of postoperative CSF rhinorrhoea in the endonasal transsphenoidal approach (TSA) and the expanded endonasal approach (EEA) for skull-base tumors.MethodsA prospective observational cohort study of 30 centres performing endonasal skull-base neurosurgery in the UK and Ireland (representing 91% of adult units). Patients were identified for 6 months and followed up for 6 months. Data collection and analysis was guided by our published protocol and pilot studies. Descriptive statistics, univariate and multivariable logistic regression models were used for analysis.ResultsA total of 866 patients were included - 726 TSA (84%) and 140 EEA (16%). There was significant heterogeneity in repair protocols across centres. In TSA cases, nasal packing (519/726, 72%), tissue glues (474/726, 65%) and hemostatic agents (439/726, 61%) were the most common skull base repair techniques. Comparatively, pedicled flaps (90/140, 64%), CSF diversion (38/140, 27%), buttresses (17/140, 12%) and gasket sealing (11/140, 9%) were more commonly used in EEA cases. CSF rhinorrhoea (biochemically confirmed or requiring re-operation) occurred in 3.9% of TSA (28/726) and 7.1% of EEA (10/140) cases. A significant number of patients with CSF rhinorrhoea (15/38, 39%) occurred when no intraoperative CSF leak was reported. On multivariate analysis, there may be marginal benefits with using tissue glues in TSA (OR: 0.2, CI: 0.1-0.7, p

Summary: Background: Cauda equina syndrome (CES) results from nerve root compression in the lumbosacral spine, usually due to a prolapsed intervertebral disc. Evidence for management of CES is limited by its infrequent occurrence and lack of standardised clinical definitions and outcome measures. Methods: This is a prospective multi-centre observational cohort study of adults with CES in the UK. We assessed presentation, investigation, management, and all Core Outcome Set domains up to one year post-operatively using clinician and participant reporting. Univariable and multivariable associations with the Oswestry Disability Index (ODI) and urinary outcomes were investigated. Findings: In 621 participants with CES, catheterisation for urinary retention was required pre-operatively in 31% (191/615). At discharge, only 13% (78/616) required a catheter. Median time to surgery from symptom onset was 3 days (IQR:1–8) with 32% (175/545) undergoing surgery within 48 h. Earlier surgery was associated with catheterisation (OR:2.2, 95%CI:1.5–3.3) but not with admission ODI or radiological compression. In multivariable analyses catheter requirement at discharge was associated with pre-operative catheterisation (OR:10.6, 95%CI:5.8–20.4) and one-year ODI was associated with presentation ODI (r = 0.3, 95%CI:0.2–0.4), but neither outcome was associated with time to surgery or radiological compression. Additional healthcare services were required by 65% (320/490) during one year follow up. Interpretation: Post-operative functional improvement occurred even in those presenting with urinary retention. There was no association between outcomes and time to surgery in this observational study. Significant healthcare needs remained post-operatively. Funding: DCN Endowment Fund funded study administration. Castor EDC provided database use. No other study funding was received.

BackgroundChronic subdural hematoma (CSDH) is a collection of blood and fluid that arises on the brain surface due to a combination of trauma and/or inflammation. The mainstay of treatment is surgical drainage, but CSDH can recur. Dexamethasone has been shown to reduce CSDH recurrence, but its mechanism of action has not been fully elucidated. Understanding the inflammatory mediators driving CSDH formation and recurrence and how dexamethasone alters this can help develop new therapeutic strategies.MethodsA subgroup of adult patients recruited to the Dex-CSDH trial, randomized to dexamethasone or placebo, who had surgery for their CSDH, were included. CSDH fluid and peripheral blood were collected intraoperatively, from post-operative drains and operated recurrences. Samples were analyzed using a 12-plex panel of inflammatory mediators. Clinical patient data were also reviewed.ResultsA total of 52 patients, with a mean age of 76 years, were included. Five recurrent CSDHs occurred. Vascular endothelial growth factor (VEGF) had the highest concentration across all CSDHs, and only matrix metalloproteinase (MMP)-9 had lower concentrations in CSDH compared to plasma but was increased in recurrent CSDHs. The interleukin (IL)-10 concentration was significantly lower in primary CSDHs that recurred. Most inflammatory mediators increased post-operatively, and dexamethasone significantly reduced the post-operative peak in VEGF on day 2, compared to placebo.ConclusionIt is evident that VEGF plays a critical role in the inflammatory response in CSDH. The post-operative reduction with dexamethasone could signal the mechanism by which it reduces recurrence. Novel therapies with a better side-effect profile than dexamethasone should be targeted at VEGF or potential alternatives such as IL-10 supplementation.

Introduction Fractures of the odontoid process frequently result from low impact falls in frail or older adults. These are increasing in incidence and importance as the population ages. In the UK, odontoid fractures in older adults are usually managed in hard collars to immobilise the fracture and promote bony healing. However, bony healing does not always occur in older adults, and bony healing is not associated with quality of life, functional, or pain outcomes. Further, hard collars can cause complications such as skin pressure ulcers, swallowing difficulties and difficulties with personal care. We hypothesise that management with no immobilisation may be superior to management in a hard collar for older or frail adults with odontoid fractures.Methods and analyses This is the protocol for the Duration of External Neck Stabilisation (DENS) trial—a non-blinded randomised controlled trial comparing management in a hard collar with management without a collar for older (≥65 years) or frail (Rockwood Clinical Frailty Scale ≥5) adults with a new odontoid fracture. 887 neurologically intact participants with any odontoid process fracture type will be randomised to continuing with a hard collar (standard care) or removal of the collar (intervention). The primary outcome is quality of life measured using the EQ-5D-5L at 12 weeks. Secondary outcomes include pain scores, neck disability index, health and social care use and costs, and mortality.Ethics and dissemination Informed consent for participation will be sought from those able to provide it. We will also include those who lack capacity to ensure representativeness of frail and acutely unwell older adults. Results will be disseminated via scientific publication, lay summary, and visual abstract. The DENS trial received a favourable ethical opinion from the Scotland A Research Ethics Committee (21/SS/0036) and the Leeds West Research Ethics Committee (21/YH/0141).Trial registration number NCT04895644.

Abstract 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 6-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 2-week course of dexamethasone following a CSDH. Seven hundred fifty patients were randomised to either dexamethasone or placebo. The primary outcome is the modified Rankin Scale at 6 months which is dichotomised to favourable (a score of 0–3) versus unfavourable (a score of 4–6). Conclusions This paper and the accompanying additional material describe the statistical analysis plan for the trial. Trial registration ISRCTN, ISRCTN80782810. Registered on 7 November 2014. http://www.isrctn.com/ISRCTN80782810. EudraCT, 2014-004948-35. Registered on 20 March 2015.

Abstract 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.

Introduction Integrated care pathways (ICPs) are a pre-defined framework of evidence based, multidisciplinary practice for specific patients. They have the potential to enhance continuity of care, patient safety, patient satisfaction, efficiency gains, teamwork and staff education. In order to inform the development of neurosurgical ICPs in the future, we performed a systematic review to aggregate examples of neurosurgical ICP, to consider their impact and design features that may be associated with their success. Methods Electronic databases MEDLINE, EMBASE, and CENTRAL were searched for relevant literature published from date of inception to July 2020. Primary studies reporting details of neurosurgical ICPs, across all pathologies and age groups were eligible for inclusion. Patient outcomes in each case were also recorded. Results Twenty-four studies were included in our final dataset, from the United States, United Kingdom, Italy, China, Korea, France, Netherlands and Switzerland, and a number of sub-specialties. 3 for cerebrospinal fluid diversion, 1 functional, 2 neurovascular, 1 neuro-oncology, 2 paediatric, 2 skull base, 10 spine, 1 for trauma, 2 miscellaneous (other craniotomies). All were single centre studies with no regional or national examples. Thirteen were cohort studies while 11 were case series which lacked a control group. Effectiveness was typically evaluated using hospital or professional performance metrics, such as length of stay (n = 11, 45.8%) or adverse events (n = 17, 70.8%) including readmission, surgical complications and mortality. Patient reported outcomes, including satisfaction, were evaluated infrequently (n = 3, 12.5%). All studies reported a positive impact. No study reported how the design of the ICP was informed by published literature or other methods Conclusions ICPs have been successfully developed across numerous neurosurgical sub-specialities. However, there is often a lack of clarity over their design and weaknesses in their evaluation, including an underrepresentation of the patient’s perspective.

Abstract Chronic subdural haematoma (CSDH) is an encapsulated collection of blood and fluid on the surface of the brain. Historically considered a result of head trauma, recent evidence suggests there are more complex processes involved. Trauma may be absent or very minor and does not explain the progressive, chronic course of the condition. This review focuses on several key processes involved in CSDH development: angiogenesis, fibrinolysis and inflammation. The characteristic membrane surrounding the CSDH has been identified as a source of fluid exudation and haemorrhage. Angiogenic stimuli lead to the creation of fragile blood vessels within membrane walls, whilst fibrinolytic processes prevent clot formation resulting in continued haemorrhage. An abundance of inflammatory cells and markers have been identified within the membranes and subdural fluid and are likely to contribute to propagating an inflammatory response which stimulates ongoing membrane growth and fluid accumulation. Currently, the mainstay of treatment for CSDH is surgical drainage, which has associated risks of recurrence requiring repeat surgery. Understanding of the underlying pathophysiological processes has been applied to developing potential drug treatments. Ongoing research is needed to identify if these therapies are successful in controlling the inflammatory and angiogenic disease processes leading to control and resolution of CSDH.

After publication of the original article [1], the authors notified that that one of the BNTRC institutional collaborator names was misspelled.