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Abstract Background Chronic subdural haematoma (CSDH) drainage is a common neurosurgical procedure. CSDHs cause excess mortality, which is exacerbated by frailty. Sarcopenia contributes to frailty – its key component, low muscle mass, can be assessed using cross‐sectional imaging. We aimed to examine the prognostic role of temporal muscle thickness (TMT) measured from preoperative computed tomography head scans among patients undergoing surgical CSDH drainage. Methods We retrospectively identified all patients who underwent CSDH drainage within 1 year of February 2019. We measured their mean TMT from preoperative computed tomography scans, tested the reliability of these measurements, and evaluated their prognostic value for postoperative survival. Results One hundred and eighty‐eight (122, 65% males) patients (median age 78 years, IQR 70–85 years) were included. Thirty‐four (18%) patients died within 2 years, and 51 (27%) died at a median follow‐up of 39 months (IQR 34–42 months). Intra‐ and inter‐observer reliability of TMT measurements was good‐to‐excellent (ICC 0.85–0.97, P

Background Traumatic brain injury (TBI) is associated with an increased risk of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). We aimed to identify predictors and develop models for the prediction of depression and PTSD symptoms at 6 months post-TBI.Methods We analysed data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury study. We used linear regression to model the relationship between predictors and depression (Patient Health Questionnaire-9) and PTSD symptoms (PTSD Checklist for Diagnostic and Statistical Manual for Mental Health Disorders Fifth Edition). Predictors were selected based on Akaike’s Information Criterion. Additionally, we fitted logistic models for the endpoints ‘probable MDD’ and ‘probable PTSD’. We also examined the incremental prognostic value of 2–3 weeks of symptoms.Results We included 2163 adults (76% Glasgow Coma Scale=13–15). Depending on the scoring criteria, 7–18% screened positive for probable MDD and about 10% for probable PTSD. For both outcomes, the selected models included psychiatric history, employment status, sex, injury cause, alcohol intoxication and total injury severity; and for depression symptoms also preinjury health and education. The performance of the models was modest (proportion of explained variance=R2 8% and 7% for depression and PTSD, respectively). Symptoms assessed at 2–3 weeks had a large incremental prognostic value (delta R2=0.25, 95% CI 0.24 to 0.26 for depression symptoms; delta R2=0.30, 95% CI 0.29 to 0.31 for PTSD).Conclusion Preinjury characteristics, such as psychiatric history and unemployment, and injury characteristics, such as violent injury cause, can increase the risk of mental health problems after TBI. The identification of patients at risk should be guided by early screening of mental health.

Current research suggests gender (“sex assigned at birth”) differences with respect to indoor environmental conditions, indicating females are more critical and demanding towards satisfaction and preferences. The present paper analyzes the results of a subsample of a national survey completed in 375 representative dwellings in Sweden. The survey collected information on twelve comfort factors and satisfaction aspects concerning thermal comfort, indoor air quality, acoustic comfort, satisfaction with daylight, size, standard, layout, appearance, well-being, cost, and neighborhood. Advanced statistical analyses were used to investigate whether the responses of occupants experiencing similar indoor conditions (cohabitation) were different with respect to gender. The analysis did not observe any significant gender differences with respect to the ratings of indoor environments in dwellings. Males reported slightly higher satisfaction, while thermal and acoustic comfort exhibited the highest gender variability. Satisfaction aspects were generally very high, with the costs and acoustic comfort registering the highest levels of dissatisfaction. Additional analyses across various building characteristics and individual attributes (variables levels) confirmed no differences. Several hypotheses were put up to explain these results, including the extreme climatic conditions and the collaborative use of dwellings. The findings suggest that Swedish dwelling designs can provide some best practice guidance for stakeholders and practitioners elsewhere in similar climatic conditions. Future studies should confirm the present observations and the social and cultural aspects of the findings.

Summary: Background: Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes. Methods: Meta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.gov ID NCT02210221) in Europe (December 2014–December 2017) and the TRACK-TBI study in the US (March 2014–July 2018). In both cohorts, the most common causes of injury were road traffic accidents and falls. Primary outcomes, specifically probable PTSD and depression, were defined at 6 months post-injury using scores ≥33 on the PTSD Checklist-5 and ≥15 on the Patient Health Questionnaire-9, respectively. We calculated PTSD-PRS and MDD-PRS for patients aged ≥17 years who had a Glasgow Coma Scale score of 13–15 upon hospital arrival and assessed their association with PTSD and depression following TBI. We also evaluated the transferability of the findings in a cohort of African Americans. Findings: Overall, 11.8% (219/1869) and 6.7% (124/1869) patients were classified as having probable PTSD and depression, respectively. The PTSD-PRS was significantly associated with higher adjusted odds of PTSD in both cohorts, with a pooled odds ratio (OR) of 1.55 [95% confidence interval (CI) 1.30–1.84, p

Abstract Background The purpose of the current study was to adapt and explore the psychometric properties of the Oxford Happiness Questionnaire Short Form (OHQ-SF) in a Greek student sample. Aim This quantitative cross-sectional study was applied in order to translate and validate the Oxford Happiness Questionnaire Short Form (OHQ-SF) into Greek and to assess the psychometric properties. Method The English version of OHQ-SF was translated into Greek using the forward and backward translation. The sample was consisted of 88 adult students from the Public Educational Training Institution in Thessaloniki. Two self-report measures the Greek version of OHQ-SF and the Greek version of the Life Orientation Test Revised (LOT-R—to check the construct validity) were completed twice, for test and retest assessment, in full anonymity and confidentiality. Statistical analysis The psychometric properties of OHQ-SF/GR, namely the internal–external reliability and construct validity, were assessed, and the expected unidimensional structure was tested with Confirmatory Factor Analysis (CFA). Results and discussion The Greek version of OHQ-SF (OHQ-SF/GR), for both test and retest, has adequate internal reliability, satisfactory structural validity, and adequate construct validity. The CFA indicated the unidimensional structure of the OHQ-SF/GR, and the fit indexes displayed good fit with the data. One item was removed due to poor correlation with the latent factor of happiness. The current study reveals that the final seven-item OHQ-SF/GR has very satisfactory psychometric properties being useful instrument to measure happiness levels in Greek adult students and is a valid tool that can be utilised in research field.

Summary: Background: The inflammatory response in patients with traumatic brain injury (TBI) offers opportunities for stratification and intervention. Previous unselected approaches to immunomodulation in patients with TBI have not improved patient outcomes. Methods: Serum and plasma samples from two prospective, multi-centre observational studies of patients with TBI were used to discover (Collaborative European NeuroTrauma Effectiveness Research [CENTER-TBI], Europe) and validate (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI] Pilot, USA) individual variations in the immune response using a multiplex panel of 30 inflammatory mediators. Mediators that were associated with unfavourable outcomes (Glasgow outcome score-extended [GOS-E] ≤ 4) were used for hierarchical clustering to identify patients with similar signatures. Findings: Two clusters were identified in both the discovery and validation cohorts, termed early-inflammatory and pauci-inflammatory. The early-inflammatory phenotype had higher concentrations of interleukin-6 (IL-6), IL-15, and monocyte chemoattractant protein 1 (MCP1). Patients with the early-inflammatory phenotype were older and more likely to have an unfavourable GOS-E at 6 months. There were no differences in the baseline injury severity scores between patients in each phenotype. A combined IL-15 and MCP1 signature identified patients with the early-inflammatory phenotype in both cohorts. Inflammatory processes mediated outcomes in older patients with moderate-severe TBI. Interpretation: Our findings offer a precision medicine approach for future clinical trials of immunomodulation in patients with TBI, by using inflammatory signatures to stratify patients. Funding: CENTER-TBI study was supported by the European Union 7th Framework Programme. TRACK-TBI is supported by the National Institute of Neurological Disorders and Stroke.

Summary: Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury. Methods: Exposure–response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates. Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13–15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13–15 and positive CT (1.21–2.81), GCS 9–12 (1.16–2.02), GCS 3–8 (1.09–1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51–1.80) percentages of unfavourable outcome were 37–51% in the lowest quintiles of biomarker levels and reached 90–94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83–3.79), the percentages were 2–4% and 19–28% in the lowest and highest biomarker quintiles, respectively. Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity. Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.

The Greek economic crisis produced severe economic and social outcomes. A massive rescue package was conditional on implementing a Memorandum of Economic and Financial Policies agreed upon between the Greek government and the EU, European Central Bank, and the International Monetary Fund. The extremely austere fiscal consolidation and the structural reforms accompanying the Greek Economic Adjustment Programmes reduced the country’s GDP. Implementing the austerity policies on the Greek National Health System, which was already facing structural problems, reduced the quality and availability of public health care services. This paper investigates the impact of the GDP change on public healthcare expenditures (HCE) from 2000 to 2018. The empirical analysis reveals a statistically significant positive correlation between the GDP per capita and public healthcare expenditure (HCE) from 2000 to 2014 while the effect of GDP on HCE after the 2015 remains unchanged. This paper contributes to the field’s literature since it determines the impact of GDP on public HCE, specifically matched with empirical results to derive conclusive answers.

The aim of this study was to explore the application of computational models for the analysis of histopathological images in the context of colon cancer. A comprehensive dataset of colon cancer images annotated into eight distinct categories based on their representation of cancerous cell portions was used. The primary objective was to employ various image classification algorithms to assess their efficacy in the context of cancer classification. Additionally, this study investigated the use of feature extraction techniques to derive meaningful data from the images, contributing to a more nuanced understanding of cancerous tissues, comparing the performance of different image classification algorithms in the context of colon cancer image analysis. The findings of this research suggested that XGboost provides the highest accuracy (89.79%) and could contribute to the growing body of knowledge in computational pathology. Other algorithms, such as the random forest, SVM, and CNN, also provided satisfactory results, offering insights into the effectiveness of image classification algorithms in distinguishing between different categories of cancerous cells. This work holds implications for the development of more accurate and efficient tools, underscoring the potential of computational models in enhancing the analysis of histopathological images and improving diagnostic capabilities in cancer research.

Introduction Research quality within the neurosurgical field remains suboptimal. Therefore, many studies published in the neurosurgical literature lack enough statistical power to establish the presence or absence of clinically important differences between treatment arms. The field of neurotrauma deals with additional challenges, with fewer financial incentives and restricted resources in low-income and middle-income countries with the highest burden of neurotrauma diseases. In this systematic review, we aim to estimate the prevalence of false claims of equivalence in the neurosurgical trauma literature and identify its predictive factors.Methods and analysis The Preferred Reporting Items for Systematic Review and Meta-Analyses recommendations were followed. Randomised clinical trials that enrolled only traumatic brain injury patients and investigated any type of intervention (surgical or non-surgical) will be eligible for inclusion. The MEDLINE/PubMed database will be searched for articles in English published from January 1960 to July 2020 in 15 top-ranked journals. A false claim of equivalence will be identified by insufficient power to detect a clinically meaningful effect: for categorical outcomes, a difference of at least 25% and 50%, and for continuous outcomes, a Cohen’s d of at least 0.5 and 0.8. Using the number of patients in each treatment arm and the minimum effect sizes to be detected, the power of each study will be calculated with the assumption of a two-tailed alpha that equals 0.05. Standardised differences between the groups with and without a false claim of equivalence will be calculated, and the variables with a standardised difference equal or above 0.2 and 0.5 will be considered weakly and strongly associated with false claims of equivalence, respectively. The data analysis will be blinded to the authors and institutions of the studies.Ethics and dissemination This study will not involve primary data collection. Therefore, formal ethical approval will not be required. The final systematic review will be published in a peer-reviewed journal and presented at appropriate conferences.

IntroductionTraumatic brain injury (TBI) is one of the leading causes of all injury-related deaths and disabilities in the world, especially in low to middle-income countries (LMICs) which also suffer from lower levels of funding for all levels of the health care system for patients suffering from TBI. These patients do not generally get comprehensive diagnostic workup, monitoring, or treatment, and return to work too quickly, often with undiagnosed post-traumatic deficits which in turn can lead to subsequent incidents of physical harm.MethodsHere, we share methods and results from our research project to establish innovative, simple, and scientifically based practices that dramatically leverage technology and validated testing strategies to identify post-TBI deficits quickly and accurately, to circumvent economic realities on the ground in LMICs. We utilized paper tests such as the Montreal cognitive assessment (MoCA), line-bisection, and Bell’s test. Furthermore, we combined modifications of neuroscience computer tasks to aid in assessing peripheral vision, memory, and analytical accuracies. Data from seventy-one subjects (51 patients and 20 controls, 15 females and 56 males) from 4 hospitals in Ethiopia are presented. The traumatic brain injury group consists of 17 mild, 28 moderate, and 8 severe patients (based on the initial Glasgow Comma Score). Controls are age and education-matched subjects (no known history of TBI, brain lesions, or spatial neglect symptoms).ResultsWe found these neurophysiological methods can: 1) be implemented in LMICs and 2) test impairments caused by TBI, which generally affect brain processing speed, memory, and both executive and cognitive controls.DiscussionThe main findings indicate that these examinations can identify several deficits, especially the MoCA test. These tests show great promise to assist in the evaluation of TBI patients and support the establishment of dedicated rehabilitation centers. Our next steps will be expansion of the cohort size and application of the tests to other settings.

Objectives To investigate the longitudinal trends of decompressive craniectomy (DC) following traumatic brain injury (TBI) or stroke and explore whether the timing of cranial reconstruction affected revision or removal rates using Hospital Episode Statistics (HES) between 2014 and 2019.Design Retrospective observational cohort study using HES. The time frame definitions mirror those often used in clinical practice.Setting HES data from neurosurgical centres in England.Participants HES data related to decompressive craniectomy procedures and cranioplasty following TBI or stroke between 2014 and 2019.Main outcome measures The primary outcome was the timing and rate of revision/removal compared with cranioplasty within

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 The epidemiology of traumatic brain injury (TBI) is unclear – it is estimated to affect 27–69 million individuals yearly with the bulk of the TBI burden in low-to-middle income countries (LMICs). Research has highlighted significant between-hospital variability in TBI outcomes following emergency surgery, but the overall incidence and epidemiology of TBI remains unclear. To address this need, we established the Global Epidemiology and Outcomes following Traumatic Brain Injury (GEO-TBI) registry, enabling recording of all TBI cases requiring admission irrespective of surgical treatment. Objective The GEO-TBI: Incidence study aims to describe TBI epidemiology and outcomes according to development indices, and to highlight best practices to facilitate further comparative research. Design Multi-centre, international, registry-based, prospective cohort study. Subjects Any unit managing TBI and participating in the GEO-TBI registry will be eligible to join the study. Each unit will select a 90-day study period. All TBI patients meeting the registry inclusion criteria (neurosurgical/ICU admission or neurosurgical operation) during the selected study period will be included in the GEO-TBI: Incidence. Methods All units will form a study team, that will gain local approval, identify eligible patients and input data. Data will be collected via the secure registry platform and validated after collection. Identifiers may be collected if required for local utility in accordance with the GEO-TBI protocol. Data Data related to initial presentation, interventions and short-term outcomes will be collected in line with the GEO-TBI core dataset, developed following consensus from an iterative survey and feedback process. Patient demographics, injury details, timing and nature of interventions and post-injury care will be collected alongside associated complications. The primary outcome measures for the study will be the Glasgow Outcome at Discharge Scale (GODS) and 14-day mortality. Secondary outcome measures will be mortality and extended Glasgow Outcome Scale (GOSE) at the most recent follow-up timepoint.

BackgroundDeveloping new clinical measures for degenerative cervical myelopathy (DCM) is an AO Spine RECODE-DCM Research, an international and multi-stakeholder partnership, priority. Difficulties in detecting DCM and its changes cause diagnostic and treatment delays in clinical settings and heightened costs in clinical trials due to elevated recruitment targets. Digital outcome measures can tackle these challenges due to their ability to measure disease remotely, repeatedly, and more economically. ObjectiveThe aim of this study is to assess the reliability of the MoveMed battery of performance outcome measures. MethodsA prospective observational study in decentralized secondary care was performed in England, United Kingdom. The primary outcome was to determine the test-retest reliability of the MoveMed performance outcomes using the intraclass correlation (ICC) of agreement . The secondary outcome was to determine the measurement error of the MoveMed performance outcomes using both the SE of the mean (SEM) of agreement and the smallest detectable change (SDC) of agreement . Criteria from the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) manual were used to determine adequate reliability (ie, ICC of agreement ≥0.7) and risk of bias. Disease stability was controlled using 2 minimum clinically important difference (MCID) thresholds obtained from the literature on the patient-derived modified Japanese Orthopaedic Association (p-mJOA) score, namely, MCID ≤1 point and MCID ≤2 points. ResultsIn total, 7 adults aged 59.5 (SD 12.4) years who live with DCM and possess an approved smartphone participated in the study. All tests demonstrated moderate to excellent test-retest coefficients and low measurement errors. In the MCID ≤1 group, ICC of agreement values were 0.84-0.94 in the fast tap test, 0.89-0.95 in the hold test, 0.95 in the typing test, and 0.98 in the stand and walk test. SEM of agreement values were ±1 tap, ±1%-3% stability score points, ±0.06 keys per second, and ±10 steps per minute, respectively. SDC of agreement values were ±3 taps, ±4%-7% stability score points, ±0.2 keys per second, and ±27 steps per minute, respectively. In the MCID ≤2 group, ICC of agreement values were 0.61-0.91, 0.75-0.77, 0.98, and 0.62, respectively; SEM of agreement values were ±1 tap, ±2%-4% stability score points, ±0.06 keys per second, and ±10 steps per minute, respectively; and SDC of agreement values were ±3-7 taps, ±7%-10% stability score points, ±0.2 keys per second, and ±27 steps per minute, respectively. Furthermore, the fast tap, hold, and typing tests obtained sufficient ratings (ICC of agreement ≥0.7) in both MCID ≤1 and MCID ≤2 groups. No risk of bias factors from the COSMIN Risk of Bias checklist were recorded. ConclusionsThe criteria from COSMIN provide “very good” quality evidence of the reliability of the MoveMed tests in an adult population living with DCM.

Objective The objective of this study is to determine research priorities for the management of major trauma, representing the shared priorities of patients, their families, carers and healthcare professionals.Design/setting An international research priority-setting partnership.Participants People who have experienced major trauma, their carers and relatives, and healthcare professionals involved in treating patients after major trauma. The scope included chest, abdominal and pelvic injuries as well as major bleeding, multiple injuries and those that threaten life or limb.Methods A multiphase priority-setting exercise was conducted in partnership with the James Lind Alliance over 24 months (November 2021–October 2023). An international survey asked respondents to submit their research uncertainties which were then combined into several indicative questions. The existing evidence was searched to ensure that the questions had not already been sufficiently answered. A second international survey asked respondents to prioritise the research questions. A final shortlist of 19 questions was taken to a stakeholder workshop, where consensus was reached on the top 10 priorities.Results A total of 1572 uncertainties, submitted by 417 respondents (including 132 patients and carers), were received during the initial survey. These were refined into 53 unique indicative questions, of which all 53 were judged to be true uncertainties after reviewing the existing evidence. 373 people (including 115 patients and carers) responded to the interim prioritisation survey and 19 questions were taken to a final consensus workshop between patients, carers and healthcare professionals. At the final workshop, a consensus was reached for the ranking of the top 10 questions.Conclusions The top 10 research priorities for major trauma include patient-centred questions regarding pain relief and prehospital management, multidisciplinary working, novel technologies, rehabilitation and holistic support. These shared priorities will now be used to guide funders and teams wishing to research major trauma around the globe.

Abstract Background The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. Methods A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. Results A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). Conclusions This consensus provides practical recommendations to support a clinician’s decision making in the management of tSCI polytrauma patients.

Objective We aim to compare the effectiveness of dural closure techniques in preventing cerebrospinal fluid (CSF) leaks following surgery for intradural lesions and seek to identify additional factors associated with CSF leaks. Surgical management of spinal intradural lesions involves durotomy which requires a robust repair to prevent postoperative CSF leakage. The ideal method of dural closure and the efficacy of sealants has not been established in literature. Methods We performed a retrospective analysis of all intradural spinal cases performed at a tertiary spine centre from 1 April 2015 to 29 January 2020 and collected data on patient bio-profile, dural repair technique, and CSF leak rates. Multivariate analysis was performed to identify predictors for postoperative CSF leak. Results A total of 169 cases were reported during the study period. There were 15 cases in which postoperative CSF leak was reported (8.87%). Multivariate analysis demonstrated that patient age (odds ratio [OR], 0.942; 95% confidence interval [CI], 0.891–0.996), surgical indication listed in the “others” category (OR, 44.608; 95% CI, 1.706–166.290) and dural closure with suture, sealant and patch (OR, 22.235; 95% CI, 2.578–191.798) were factors associated with CSF leak. Postoperative CSF leak was associated with the risk of surgical site infection with a likelihood ratio of 8.704 (χ² (1) =14.633, p < 0.001). Conclusion Identifying predictors for CSF leaks can assist in the counselling of patients with regard to surgical risk and expected postoperative recovery.

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.

Within both the cyber kill chain and MITRE ATT&CK frameworks, Lateral Movement (LM) is defined as any activity that allows adversaries to progressively move deeper into a system in seek of high-value assets. Although this timely subject has been studied in the cybersecurity literature to a significant degree, so far, no work provides a comprehensive survey regarding the identification of LM from mainly an Intrusion Detection System (IDS) viewpoint. To cover this noticeable gap, this work provides a systematic, holistic overview of the topic, not neglecting new communication paradigms, such as the Internet of Things (IoT). The survey part, spanning a time window of eight years and 53 articles, is split into three focus areas, namely, Endpoint Detection and Response (EDR) schemes, machine learning oriented solutions, and graph-based strategies. On top of that, we bring to light interrelations, mapping the progress in this field over time, and offer key observations that may propel LM research forward.

Abstract Background Image optimization is a key step in clinical nuclear medicine, and phantoms play an essential role in this process. However, most phantoms do not accurately reflect the complexity of human anatomy, and this presents a particular challenge when imaging endocrine glands to detect small (often subcentimeter) tumors. To address this, we developed a novel phantom for optimization of positron emission tomography (PET) imaging of the human pituitary gland. Using radioactive 3D printing, phantoms were created which mimicked the distribution of 11C-methionine in normal pituitary tissue and in a small tumor embedded in the gland (i.e., with no inactive boundary, thereby reproducing the in vivo situation). In addition, an anatomical phantom, replicating key surrounding structures [based on computed tomography (CT) images from an actual patient], was created using material extrusion 3D printing with specialized filaments that approximated the attenuation properties of bone and soft tissue. Results The phantom enabled us to replicate pituitary glands harboring tumors of varying sizes (2, 4 and 6 mm diameters) and differing radioactive concentrations (2 ×, 5 × and 8 × the normal gland). The anatomical phantom successfully approximated the attenuation properties of surrounding bone and soft tissue. Two iterative reconstruction algorithms [ordered subset expectation maximization (OSEM); Bayesian penalized likelihood (BPL)] with a range of reconstruction parameters (e.g., 3, 5, 7 and 9 OSEM iterations with 24 subsets; BPL regularization parameter (β) from 50 to 1000) were tested. Images were analyzed quantitatively and qualitatively by eight expert readers. Quantitatively, signal was the highest using BPL with β = 50; noise was the lowest using BPL with β = 1000; contrast was the highest using BPL with β = 100. The qualitative review found that accuracy and confidence were the highest when using BPL with β = 400. Conclusions The development of a bespoke phantom has allowed the identification of optimal parameters for molecular pituitary imaging: BPL reconstruction with TOF, PSF correction and a β value of 400; in addition, for small (

Radiation therapy (RT) treatment for head and neck cancer has been associated with dysphagia manifestation leading to worse outcomes and decrease in life quality. In this study, we investigated factors leading to dysphagia and treatment prolongation in patients with primaries arising from oral cavity or oropharynx that were submitted to radiation therapy concurrently with chemotherapy. The records of patients with oral cavity or oropharyngeal cancer that received RT treatment to the primary and bilateral neck lymph nodes concurrently with chemotherapy were retrospectively reviewed. Logistic regression models were used to analyze the potential correlation between explanatory variables and the primary (dysphagia ≥ 2) and secondary (prolongation of total treatment duration ≥ 7 days) outcomes of interest. The Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) were used to evaluate dysphagia. A total of 160 patients were included in the study. Age mean was 63.31 (SD = 8.24). Dysphagia grade ≥ 2 was observed in 76 (47.5%) patients, while 32 (20%) experienced treatment prolongation ≥ 7 days. The logistic regression analysis showed that the volume in the primary site of disease that received dose ≥ 60 Gy (≥118.75 cc, p < 0.001, (OR = 8.43, 95% CI [3.51–20.26]) and mean dose to the pharyngeal constrictor muscles > 40.6 Gy (p < 0.001, OR = 11.58, 95% CI [4.84–27.71]) were significantly associated with dysphagia grade ≥ 2. Treatment prolongation ≥ 7 days was predicted by higher age (p = 0.007, OR = 1.079, 95% CI [1.021–1.140]) and development of grade ≥ 2 dysphagia (p = 0.005, OR = 4.02, 95% CI [1.53–10.53]). In patients with oral cavity or oropharyngeal cancer that receive bilateral neck irradiation concurrently with chemotherapy, constrictors mean dose and the volume in the primary site receiving ≥ 60 Gy should be kept below 40.6 Gy and 118.75 cc, respectively, whenever possible. Elderly patients or those that are considered at high risk for dysphagia manifestation are more likely to experience treatment prolongation ≥ 7 days and they should be closely monitored during treatment course for nutritional support and pain management.

Summary: Background: Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy. Methods: We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014–2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Findings: Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12–26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were trebled (adjusted median odds ratio 2.7, p

In the present paper, we develop a non-homogeneous semi-Markov reward model, deriving expressions for a healthcare system’s expected structure along with the expected costs generated by medical services and patients’ holding times in the states. We provide a novel definition and investigation for states’ availability, which is critical for capacity planning based on service demand in an environment of limited resources. The study is based on patients’ mobility through hospital care, where each patient spends an amount of time in every state of the hospital (emergency room, short-term acute care, hospitalization, surgery room, and intensive care unit). Multiple outcomes, such as discharge or death, can also be taken into account. We envisage a situation where any discharges are immediately replaced by a number of new admissions that carry on the pathways of the patients who exit. By assuming an expanding system, the new idea of states’ inflows is considered due to new patients who create pathways through hospital care, along with internal entrances. The theoretical results are illustrated numerically with simulated hospital data informed by aggregated public data of the Greek public health sector. The framework can be used for both strategic planning and cost evaluation purposes for hospital resources.

Introduction: Planning cranioplasty (CPL) in patients with suspected or proven post-traumatic hydrocephalus (PTH) poses a significant management challenge due to a lack of clear guidance. Research question: This project aims to create a European document to improve adherence and adapt to local protocols based on available resources and national health systems. Methods: After a thorough non-systematic review, a steering committee (SC) formed a European expert panel (EP) for a two-round questionnaire using the Delphi method. The questionnaire employed a 9-point Likert scale to assess the appropriateness of statements inherent to two sections: ''Diagnostic criteria for PTH'' and ''Surgical strategies for PTH and cranial reconstruction.'' Results: The panel reached a consensus on 29 statements. In the ''Diagnostic criteria for PTH'' section, five statements were deemed ''appropriate'' (consensus 74.2−90.3 %), two were labeled ''inappropriate,'' and seven were marked as ''uncertain.''In the ''Surgical strategies for PTH and cranial reconstruction'' section, four statements were considered ''appropriate'' (consensus 74.2−90.4 %), six were ''inappropriate,'' and five were ''uncertain.'' Discussion and conclusion: Planning a cranioplasty alongside hydrocephalus remains a significant challenge in neurosurgery. Our consensus conference suggests that, in patients with cranial decompression and suspected hydrocephalus, the most suitable diagnostic approach involves a combination of evolving clinical conditions and neuroradiological imaging. The recommended management sequence prioritizes cranial reconstruction, with the option of a ventriculoperitoneal shunt when needed, preferably with a programmable valve. We strongly recommend to adopt local protocols based on expert consensus, such as this, to guide patient care.

ObjectivesTo assess whether different cervical spine immobilisation strategies (full immobilisation, movement minimisation or no immobilisation), impact neurological and/or other outcomes for patients with suspected cervical spinal injury in the pre-hospital and emergency department setting.DesignSystematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sourcesMEDLINE, EMBASE, CINAHL, Cochrane Library and two research registers were searched until September 2023.Eligibility criteriaAll comparative studies (prospective or retrospective) that examined the potential benefits and/or harms of immobilisation practices during pre-hospital and emergency care of patients with a potential cervical spine injury (pre-imaging) following blunt trauma.Data extraction and synthesisTwo authors independently selected and extracted data. Risk of bias was appraised using the Cochrane ROBINS-I tool for non-randomised studies. Data were synthesised without meta-analysis.ResultsSix observational studies met the inclusion criteria. The methodological quality was variable, with most studies having serious or critical risk of bias. The effect of cervical spine immobilisation practices such as full immobilisation or movement minimisation during pre-hospital and emergency care did not show clear evidence of benefit for the prevention of neurological deterioration, spinal injuries and death compared with no immobilisation. However, increased pain, discomfort and anatomical complications were associated with collar application during immobilisation.ConclusionsDespite the limited evidence, weak designs and limited generalisability, the available data suggest that pre-hospital cervical spine immobilisation (full immobilisation or movement minimisation) was of uncertain value due to the lack of demonstrable benefit and may lead to potential complications and adverse outcomes. High-quality randomised comparative studies are required to address this important question.Trial registrationPROSPERO REGISTRATION Fiona Lecky, Abdullah Pandor, Munira Essat, Anthea Sutton, Carl Marincowitz, Gordon Fuller, Stuart Reid, Jason Smith. A systematic review of cervical spine immobilisation following blunt trauma in pre-hospital and emergency care. PROSPERO 2022 CRD42022349600 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022349600.

Introduction: Neurosurgery is one of the rapidly evolving specialities of medical science, where the neurosurgeons have to provide evidence-based interventions in life threatening conditions maintaining the ethical standards. Research question: This narrative review sheds light on the current hindrances of the ethical aspects of neurosurgical practice in low and middle-income countries (LMICs) and provide some feasible solutions for future. Material and methods: A literature search was conducted using PubMed, Scopus and ISI web of knowledge focused on articles in English with the words “medical ethics” together with the words “neurosurgery”, “ethical practice”, “low and middle-income countries”, “surgical innovation”, “randomized clinical trials” and “outcome” alone or in combination. Results: Due to the lack of neurosurgeons and essential infrastructures in LMICs, the practical application of medical ethics is more complicated in the field of neurosurgery. Main obstacles to conduct preclinical and clinical research in the LMICs are the lack of proper ethics committees, quality data, trained manpower and sufficient research funding. Implementation of randomized clinical trials (RCTs) is also difficult for the neurosurgeons working in LMICs. Discussion and conclusion: To improve the situation, socio-economic development, including educating the citizens of these countries about their rights, functional regulatory bodies like medical and dental councils, teaching the neurosurgeons about the internationally recognized medical ethics, quality control regulations by the ministry of health and welfare, and more funding for the health care sectors are urgently needed. Global collaboration is needed to help the LMICs to provide their patients international but “customized” standard care.

Background: Traumatic brain injury is a disease with high mortality with increased intracranial pressure included in the emergency department. Neuroimaging and intracranial pressure monitoring are limited in resource-limited settings. Optic nerve sheath diameter measurement to assess intracranial pressure indirectly using point-of-care ultrasound is appealing in diagnostics and decision-making. Objectives: We plan to evaluate the utility of point-of-care ultrasound on optic nerve sheath diameter role in traumatic brain injury patients. In these patients, optic nerve sheath diameter measurement was performed immediately postoperatively and 24 h later by trained residents. The procedure was repeated if any change in clinical status was observed. Results: A total of 50 patients were enrolled. Twenty-one patients underwent neurosurgical intervention. Three patients died in hospital. Eighteen patients had optic nerve sheath diameters less than 5 mm, 20 patients had optic nerve sheath diameter between 5 mm and 6 mm, and 12 patients had optic nerve sheath diameter > 6 mm. In 2 patients with changes in clinical condition, the repeat optic nerve sheath diameter assessment showed an increase in optic nerve sheath diameter. Conclusion: Despite limitations, trained health care providers can perform optic nerve sheath diameter. Longer training time and quality assurance are needed to appreciate the impact.

Objective To establish a consensus on the structure and process of healthcare services for patients with concussion in England to facilitate better healthcare quality and patient outcome.Design This consensus study followed the modified Delphi methodology with five phases: participant identification, item development, two rounds of voting and a meeting to finalise the consensus statements. The predefined threshold for agreement was set at ≥70%.Setting Specialist outpatient services.Participants Members of the UK Head Injury Network were invited to participate. The network consists of clinical specialists in head injury practising in emergency medicine, neurology, neuropsychology, neurosurgery, paediatric medicine, rehabilitation medicine and sports and exercise medicine in England.Primary outcome measure A consensus statement on the structure and process of specialist outpatient care for patients with concussion in England.Results 55 items were voted on in the first round. 29 items were removed following the first voting round and 3 items were removed following the second voting round. Items were modified where appropriate. A final 18 statements reached consensus covering 3 main topics in specialist healthcare services for concussion; care pathway to structured follow-up, prognosis and measures of recovery, and provision of outpatient clinics.Conclusions This work presents statements on how the healthcare services for patients with concussion in England could be redesigned to meet their health needs. Future work will seek to implement these into the clinical pathway.

Abstract Background Severe traumatic brain-injured (TBI) patients should be primarily admitted to a hub trauma center (hospital with neurosurgical capabilities) to allow immediate delivery of appropriate care in a specialized environment. Sometimes, severe TBI patients are admitted to a spoke hospital (hospital without neurosurgical capabilities), and scarce data are available regarding the optimal management of severe isolated TBI patients who do not have immediate access to neurosurgical care. Methods A multidisciplinary consensus panel composed of 41 physicians selected for their established clinical and scientific expertise in the acute management of TBI patients with different specializations (anesthesia/intensive care, neurocritical care, acute care surgery, neurosurgery and neuroradiology) was established. The consensus was endorsed by the World Society of Emergency Surgery, and a modified Delphi approach was adopted. Results A total of 28 statements were proposed and discussed. Consensus was reached on 22 strong recommendations and 3 weak recommendations. In three cases, where consensus was not reached, no recommendation was provided. Conclusions This consensus provides practical recommendations to support clinician’s decision making in the management of isolated severe TBI patients in centers without neurosurgical capabilities and during transfer to a hub center.

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.

Low-rate Denial of Service (LDoS) attacks are today considered one of the biggest threats against modern data centers and industrial infrastructures. Unlike traditional Distributed Denial of Service (DDoS) attacks that are mainly volumetric, LDoS attacks exhibit a very small network footprint, and therefore can easily elude standard detection and defense mechanisms. This work introduces a defense strategy that may prove particularly effective against attacks that are based on long-lived connections, an inherent trait of LDoS attacks. Our approach is based on iteratively partitioning the active connections of a victim server across a number of replica servers, and then re-evaluating the health status of each replica instance. At its core, this approach relies on live migration and containerization technologies. The main advantage of the proposed approach is that it can discover and isolate malicious connections with virtually no information about the type and characteristics of the performed attack. Additionally, while the defense takes place, there is little to no indication of the fact to the attacker. We assess various rudimentary schemes to quantify the scalability of our approach. The results from the simulations indicate that it is possible to save the vast majority of the benign connections (80%) in less than 5 min.

The aim of the article is to analyze the perceived thermal comfort and indoor air quality of occupants and establish associations between these responses and the building-related, occupant-related characteristics, and environmental parameters of residential buildings (a total of 38 variables). The analysis is focused on the Swedish building stock as investigated during the latest national survey in 2008. The analysis covers 1035 residential buildings (multifamily and single-family dwellings). Analytical statistical analysis has been conducted, and logistic regression models have also been developed for the identification of statistically significant covariates. The analysis showed that users in this study demonstrated a significantly positive response to perceived thermal comfort and indoor air quality conditions. Perceived ratings were also highly correlated with each other. As the regression models indicated, the majority of the significant variables were related to the buildings. Nevertheless, this study also underscores the significance of contextual occupant attributes and behaviors as a crucial element influencing the subjective perception of indoor environments. Policymakers, guided by these insights, are encouraged to integrate considerations of occupant attributes into design and urban planning.

Anxiety, depression, and psychological stress were the most common mental health issues that surfaced during and after the COVID-19 lockdowns. The aim of this paper is to investigate the psychological impact of the second COVID-19 lockdown on the Greek population. A cross-sectional anonymous study was designed, which measured perceived stress, depression symptoms, physical activity, and quality of life. The sample was collected during the period of the second lockdown and consisted of 330 adult individuals (219 females and 111 males) with a mean age of 34.3 years, who were located in Greece. Four scales were applied to measure the constructs, the Perceived Stress Scale (PSS-14), Beck’s Depression Inventory (BDI), Quality of Life-BREF (WHOQOL-BREF), and the International Physical Activity Questionnaire (IPAQ). The main findings suggest that depression and perceived stress were more prevalent during the second lockdown compared to previous time periods. The psychological impact was elevated for women and younger individuals. Unemployed people dealt with more stress compared to full-time working individuals. The two quality-of-life domains, physical and psychological health, were negatively correlated with perceived stress and depression. We suggest targeted interventions in order to support the most vulnerable groups and enhance their well-being.

Background: The epidemiology of traumatic brain injury (TBI) is unclear – it is estimated to affect 27–69 million individuals yearly with the bulk of the TBI burden in low-to-middle income countries (LMICs). Research has highlighted significant between-hospital variability in TBI outcomes following emergency surgery, but the overall incidence and epidemiology of TBI remains unclear. To address this need, we established the Global Epidemiology and Outcomes following Traumatic Brain Injury (GEO-TBI) registry, enabling recording of all TBI cases requiring admission irrespective of surgical treatment. Objective: The GEO-TBI: Incidence study aims to describe TBI epidemiology and outcomes according to development indices, and to highlight best practices to facilitate further comparative research. Design: Multi-centre, international, registry-based, prospective cohort study. Subjects: Any unit managing TBI and participating in the GEO-TBI registry will be eligible to join the study. Each unit will select a 90-day study period. All TBI patients meeting the registry inclusion criteria (neurosurgical/ICU admission or neurosurgical operation) during the selected study period will be included in the GEO-TBI: Incidence. Methods: All units will form a study team, that will gain local approval, identify eligible patients and input data. Data will be collected via the secure registry platform and validated after collection. Identifiers may be collected if required for local utility in accordance with the GEO-TBI protocol. Data: Data related to initial presentation, interventions and short-term outcomes will be collected in line with the GEO-TBI core dataset, developed following consensus from an iterative survey and feedback process. Patient demographics, injury details, timing and nature of interventions and post-injury care will be collected alongside associated complications. The primary outcome measures for the study will be the Glasgow Outcome at Discharge Scale (GODS) and 14-day mortality. Secondary outcome measures will be mortality and extended Glasgow Outcome Scale (GOSE) at the most recent follow-up timepoint.

Abstract Background Pituitary adenomas (PA) affect ~ 1:1200 of the population and can cause a wide range of symptoms due to hormone over-secretion, loss of normal pituitary gland function and/or compression of visual pathways, resulting in significantly impaired quality of life. Surgery is potentially curative if the location of the adenoma can be determined. However, standard structural (anatomical) imaging, in the form of MRI, is unable to locate all tumors, especially microadenomas (

Extracorporeal membrane oxygenation (ECMO) is used for the management of severe respiratory and cardiac failure and as a bridge to achieve definite treatment or transplantation. ECMO-associated coagulopathy (EAC) is a frequent complication leading to high rates of thrombosis or severe haemorrhage, contributing to morbidity and mortality among patients. Understanding the pathophysiology of EAC is substantial for effectively managing patients on ECMO. We analyse the underlying mechanism of EAC and discuss the monitoring of the coagulation profile, combining the viscoelastic point-of-care assays with the conventional coagulation laboratory tests.

The present study aims to evaluate the accuracy of the prognostic discrimination and prediction of the short-term mortality of the Marshall computed tomography (CT) classification and Rotterdam and Helsinki CT scores in a cohort of TBI patients from a low- to middle-income country. This is a post hoc analysis of a previously conducted prospective cohort study conducted in a university-associated, tertiary-level hospital that serves a population of >12 million in Brazil. Marshall CT class, Rotterdam and Helsinki scores, and their components were evaluated in the prediction of 14-day and in-hospital mortality using Nagelkerk's pseudo-R2 and area under the receiver operating characteristic curve. Multi-variate regression was performed using known outcome predictors (age, Glasgow Coma Scale, pupil response, hypoxia, hypotension, and hemoglobin values) to evaluate the increase in variance explained when adding each of the CT classification systems. Four hundred forty-seven patients were included. Mean age of the patient cohort was 40 (standard deviation, 17.83) years, and 85.5% were male. Marshall CT class was the least accurate model, showing pseudo-R2 values equal to 0.122 for 14-day mortality and 0.057 for in-hospital mortality, whereas Rotterdam CT scores were 0.245 and 0.194 and Helsinki CT scores were 0.264 and 0.229. The AUC confirms the best prediction of the Rotterdam and Helsinki CT scores regarding the Marshall CT class, which presented greater discriminative ability. When associated with known outcome predictors, Marshall CT class and Rotterdam and Helsinki CT scores showed an increase in the explained variance of 2%, 13.4%, and 21.6%, respectively. In this study, Rotterdam and Helsinki scores were more accurate models in predicting short-term mortality. The study denotes a contribution to the process of external validation of the scores and may collaborate with the best risk stratification for patients with this important pathology.

BackgroundCore outcome sets (COSs) are important and necessary as they help standardize reporting in research studies. Cranioplasty following traumatic brain injury (TBI) or stroke is becoming increasingly common, leading to an ever-growing clinical and research interest, especially regarding the optimal material, cost-effectiveness, and timing of cranioplasty concerning neurological recovery and complications. Consequently, heterogeneous reporting of outcomes from such diverse studies has led to limited meta-analysis ability and an ongoing risk of outcome reporting bias. This study aims to define a standardized COS for reporting in all future TBI and stroke cranioplasty studies. ObjectiveThis study has four aims: (1) undertake a systematic review to collate the most current outcome measures used within the cranioplasty literature; (2) undertake a qualitative study to understand better the views of clinicians, patients' relatives, and allied health professionals regarding clinical outcomes following cranioplasty; (3) undertake a Delphi survey as part of the process of gaining consensus for the COS; and (4) finalize consensus through a consensus meeting resulting in the COS. MethodsAn international steering committee has been formed to guide the development of the COS. In addition, recommendations from other clinical initiatives such as COMET (Core Outcomes and Effectiveness Trials) and OMERACT (Outcome Measures in Rheumatology) have been adhered to. Phase 1 is data collection through a systematic review and qualitative study. Phase 2 is the COS development through a Delphi survey and consensus meetings with consensus definitions decided and agreed upon before the Delphi survey begins to avoid bias. ResultsPhase 1 started at the end of 2019, following ethical approval in December 2019, and the project completion date is planned for the end of 2022 or beginning of 2023. ConclusionsThis study should result in a consensus on a COS for cranioplasty, following TBI or stroke, to help standardize outcome reporting for future studies, which can be applied to future research and clinical services, help align future studies, build an increased understanding of cranioplasty and its impact on a patient’s function and recovery, and help standardize the evidence base. International Registered Report Identifier (IRRID)DERR1-10.2196/37442

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.

Wi-Fi is arguably the most proliferated wireless technology today. Due to its massive adoption, Wi-Fi deployments always remain in the epicenter of attackers and evildoers. Surprisingly, research regarding machine learning driven intrusion detection systems (IDS) that are specifically optimized to detect Wi-Fi attacks is lagging behind. On top of that, the field is dominated by false or half-true assumptions that potentially can lead to corresponding models being overfilled to certain validation datasets, simply giving the impression or illusion of high efficiency. This work attempts to provide concrete answers to the following key questions regarding IEEE 802.11 machine learning driven IDS. First, from an expert’s viewpoint and with reference to the relevant literature, what are the criteria for determining the smallest possible set of classification features, which are also common and potentially transferable to virtually any deployment types/versions of 802.11? And second, based on these features, what is the detection performance across different network versions and diverse machine learning techniques, i.e., shallow versus deep learning ones? To answer these questions, we rely on the renowned 802.11 security-oriented AWID family of datasets. In a nutshell, our experiments demonstrate that with a rather small set of 16 features and without the use of any optimization or ensemble method, shallow and deep learning classification can achieve an average F1 score of up to 99.55% and 97.55%, respectively. We argue that the suggested human expert driven feature selection leads to lightweight, deployment-agnostic detection systems, and therefore can be used as a basis for future work in this interesting and rapidly evolving field.

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

Background: There is wide-ranging published literature around cranioplasty following traumatic brain injury (TBI) and stroke, but the heterogeneity of outcomes limits the ability for meta-analysis. Consensus on appropriate outcome measures has not been reached, and given the clinical and research interest, a core outcome set (COS) would be beneficial. Objectives: To collate outcomes currently reported across the cranioplasty literature which will subsequently be used in developing a cranioplasty COS. Methods: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. All full-text English studies with more than ten patients (prospective) or more than 20 patients (retrospective) published after 1990 examining outcomes in CP were eligible for inclusion. Results: The review included 205 studies from which 202 verbatim outcomes were extracted, grouped into 52 domains, and categorised into one or more of the OMERACT 2.0 framework core area(s). The total numbers of studies that reported outcomes in the core areas are 192 (94%) pathophysiological manifestations/ 114 (56%) resource use/economic impact/ 94 (46%) life impact/mortality 20 (10%). In addition, there are 61 outcome measures used in the 205 studies across all domains. Conclusion: This study shows considerable heterogeneity in the types of outcomes used across the cranioplasty literature, demonstrating the importance and necessity of developing a COS to help standardise reporting across the literature.

An approach for preliminary aero-engine design, incorporating a mean-line code for the design of axial-flow, multi-stage compressors, is presented. The compressor mean-line code is developed and integrated within a framework for the preliminary design and assessment of aero-engine concepts. It is then combined with modules for compressor map generation, multi-point engine design, steady-state and transient engine off-design performance and aircraft mission analysis. Implementation examples are presented, demonstrating the determination of the optimal combination of compressor and engine design parameters for achieving minimum fuel burn over a specific aircraft mission, while obeying constraints that guarantee operability over the entire flight envelope. Constraints related to compressor stability during transient maneuvers between idle and static take-off conditions and engine temperature limits at maximum take-off are respected by the final design. The results demonstrate the potential for design trade-offs between engine performance at the aircraft mission level and compressor aerodynamic stability.

Abstract Background Pituitary adenomas can give rise to a variety of clinical disorders and surgery is often the primary treatment option. However, preoperative magnetic resonance imaging (MRI) does not always reliably identify the site of an adenoma. In this setting molecular (functional) imaging (e.g. 11C-methionine PET/CT) may help with tumor localisation, although interpretation of these 2D images can be challenging. 3D printing of anatomicalal models for other indications has been shown to aid surgical planning and improve patient understanding of the planned procedure. Here, we explore the potential utility of four types of 3D printing using PET/CT and co-registered MRI for visualising pituitary adenomas. Methods A 3D patient-specific model based on a challenging clinical case was created by segmenting the pituitary gland, pituitary adenoma, carotid arteries and bone using contemporary PET/CT and MR images. The 3D anatomical models were printed using VP, MEX, MJ and PBF 3D printing methods. Different anatomicalal structures were printed in color with the exception of the PBF anatomical model where a single color was used. The anatomical models were compared against the computer model to assess printing accuracy. Three groups of clinicians (endocrinologists, neurosurgeons and ENT surgeons) assessed the anatomical models for their potential clinical utility. Results All of the printing techniques produced anatomical models which were spatially accurate, with the commercial printing techniques (MJ and PBF) and the consumer printing techniques (VP and MEX) demonstrating comparable findings (all techniques had mean spatial differences from the computer model of

Introduction Nearly every field of medicine has some form of clinical practice guidelines. However, only within the past 5–10 years has the medical community acknowledged the need for well-developed guidelines tailored to the local healthcare needs and the resources available. In most low-income and middle-income countries (LMICs), healthcare workers depend on guidelines developed in high-income countries (HICs), yet many interventions validated in a HIC are ineffective when implemented in an LMIC. The variation in infrastructure, medical personnel, technology and environmental conditions exhibited in LMICs relative to HICs necessitates a careful appraisal of the evidence base used in clinical guideline recommendations. This review aims to map the use of resource-stratified guidelines across all fields of medicine. The review seeks to answer three questions for the identified guidelines: (1) what was the method of development, (2) have they been implemented and, if so, (3) have they been validated.Methods The search strategy will aim to locate studies from inception to November 2021. An initial limited search of PubMed and Scopus was undertaken to identify articles on the topic. The text words contained in the titles and abstracts of relevant articles, and the index terms used to describe the articles were used to develop a full search strategy for PubMed and Scopus. This scoping review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews. Data to be extracted from each study will include population characteristics of both developers and intended implementation population, medical specialty, validation status, method of guideline development, whether the study is consensus or evidence-based in addition to a summary of recommendations for practice.Ethics and dissemination Ethical approval is not required for this review. The plan for dissemination is to publish review findings in a peer-reviewed journal.

Introduction Glioblastoma is the most common malignant primary brain tumour with a median overall survival of 12–15 months (range 6–17 months), even with maximal treatment involving debulking neurosurgery and adjuvant concomitant chemoradiotherapy. The use of postoperative imaging to detect progression is of high importance to clinicians and patients, but currently, the optimal follow-up schedule is yet to be defined. It is also unclear how adhering to National Institute for Health and Care Excellence (NICE) guidelines—which are based on general consensus rather than evidence—affects patient outcomes such as progression-free and overall survival. The primary aim of this study is to assess MRI monitoring practice after surgery for glioblastoma, and to evaluate its association with patient outcomes.Methods and analysis ImagiNg Timing aftER surgery for glioblastoma: an eVALuation of practice in Great Britain and Ireland is a retrospective multicentre study that will include 450 patients with an operated glioblastoma, treated with any adjuvant therapy regimen in the UK and Ireland. Adult patients ≥18 years diagnosed with glioblastoma and undergoing surgery between 1 August 2018 and 1 February 2019 will be included. Clinical and radiological scanning data will be collected until the date of death or date of last known follow-up. Anonymised data will be uploaded to an online Castor database. Adherence to NICE guidelines and the effect of being concordant with NICE guidelines will be identified using descriptive statistics and Kaplan-Meier survival analysis.Ethics and dissemination Each participating centre is required to gain local institutional approval for data collection and sharing. Formal ethical approval is not required since this is a service evaluation. Results of the study will be reported through peer-reviewed presentations and articles, and will be disseminated to participating centres, patients and the public.