The Global Macroeconomic Burden of Burn Injuries.

BACKGROUND: Standardized estimates of global economic losses from burn injuries are lacking. The primary objective of this study was to determine the global macroeconomic consequences of burn injuries and their geographic distribution. METHODS: Using the Institute of Health Metrics and Evaluation database (2009 and 2019), mean and 95% uncertainty interval (UI) data on incidence, mortality, and disability-adjusted life-years (DALYs) from injuries caused by fire, heat, and hot substances were collected. Gross domestic product (GDP) data were analyzed together with DALYs to estimate macroeconomic losses globally using a value of lost welfare approach. RESULTS: There were 9 million global burn cases (95% UI, 6.8 to 11.2 million) and 111,000 deaths from burns (95% UI, 88,000 to 132,000 deaths) in 2019, representing a total of 7.5 million DALYs (95% UI, 5.8 to 9.5 million DALYs). This represented welfare losses of $112 billion (95% UI, $78 to $161 billion), or 0.09% of GDP (95% UI, 0.06% to 0.13%). Welfare losses as a share of GDP were highest in low- and middle-income countries (LMICs) of Oceania (0.24%; 95% UI, 0.09% to 0.42%) and Eastern Europe (0.24%; 95% UI, 0.19% to 0.30%) compared with high-income country regions such as Western Europe (0.06%; 95% UI, 0.04% to 0.09%). Mortality-incidence ratios were highest in LMIC regions, highlighting a lack of treatment access, with southern sub-Saharan Africa reporting a mortality-incidence ratio of 40.1 per 1000 people compared with 1.9 for Australasia. CONCLUSIONS: Burden of disease and resulting economic losses because of burn injuries are substantial worldwide and are disproportionately higher in LMICs. Possible effective solutions include targeted education, advocacy, and legislation to decrease incidence and investing in existing burn centers to improve treatment access.

Traditional Machine Learning Methods versus Deep Learning for Meningioma Classification, Grading, Outcome Prediction, and Segmentation: A Systematic Review and Meta-Analysis.

BACKGROUND: Meningiomas are common intracranial tumors. Machine learning (ML) algorithms are emerging to improve accuracy in 4 primary domains: classification, grading, outcome prediction, and segmentation. Such algorithms include both traditional approaches that rely on hand-crafted features and deep learning (DL) techniques that utilize automatic feature extraction. The aim of this study was to evaluate the performance of published traditional ML versus DL algorithms in classification, grading, outcome prediction, and segmentation of meningiomas. METHODS: A systematic review and meta-analysis were conducted. Major databases were searched through September 2021 for publications evaluating traditional ML versus DL models on meningioma management. Performance measures including pooled sensitivity, specificity, F1-score, area under the receiver-operating characteristic curve, positive and negative likelihood ratios (LR+, LR-) along with their respective 95% confidence intervals (95% CIs) were derived using random-effects models. RESULTS: Five hundred thirty-four records were screened, and 43 articles were included, regarding classification (3 articles), grading (29), outcome prediction (7), and segmentation (6) of meningiomas. Of the 29 studies that reported on grading, 10 could be meta-analyzed with 2 DL models (sensitivity 0.89, 95% CI: 0.74-0.96; specificity 0.91, 95% CI: 0.45-0.99; LR+ 10.1, 95% CI: 1.33-137; LR- 0.12, 95% CI: 0.04-0.59) and 8 traditional ML (sensitivity 0.74, 95% CI: 0.62-0.83; specificity 0.93, 95% CI: 0.79-0.98; LR+ 10.5, 95% CI: 2.91-39.5; and LR- 0.28, 95% CI: 0.17-0.49). The insufficient performance metrics reported precluded further statistical analysis of other performance metrics. CONCLUSIONS: ML on meningiomas is mostly carried out with traditional methods. For meningioma grading, traditional ML methods generally had a higher LR+, while DL models a lower LR-.

Global, Regional, and National Economic Consequences of Stroke.

BACKGROUND: An understanding of global, regional, and national macroeconomic losses caused by stroke is important for allocation of clinical and research resources. The authors investigated the macroeconomic consequences of stroke disease burden in the year 2019 in 173 countries. METHODS: Disability-adjusted life year data for overall stroke and its subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) were collected from the GBD study (Global Burden of Disease) 2019 database. Gross domestic product (GDP, adjusted for purchasing power parity [PPP]) data were collected from the World Bank; GDP and disability-adjusted life year data were combined to estimate macroeconomic losses using a value of lost welfare (VLW) approach. All results are presented in 2017 international US dollars adjusted for PPP. RESULTS: Globally, in 2019, VLW due to stroke was $2059.67 billion or 1.66% of the global GDP. Global VLW/GDP for stroke subtypes was 0.78% (VLW=$964.51 billion) for ischemic stroke, 0.71% (VLW=$882.81 billion) for intracerebral hemorrhage, and 0.17% (VLW=$212.36 billion) for subarachnoid hemorrhage. The Central European, Eastern European, and Central Asian GBD super-region reported the highest VLW/GDP for stroke overall (3.01%), ischemic stroke (1.86%), and for subarachnoid hemorrhage (0.26%). The Southeast Asian, East Asian, and Oceanian GBD super-region reported the highest VLW/GDP for intracerebral hemorrhage (1.48%). CONCLUSIONS: The global macroeconomic consequences related to stroke are vast even when considering stroke subtypes. The present quantification may be leveraged to help justify increased spending of finite resources on stroke in an effort to improve outcomes for patients with stroke globally.

External ventricular drains and risk of freehand placement: A systematic review and meta-analysis.

OBJECTIVE: External ventricular drains (EVDs) are used to monitor and treat elevated intracranial pressure. EVDs are often placed blindly without the use of imaging guidance, and successful placement with respect to pass attempts and final catheter location may suffer as a result of this freehand technique. METHODS: A systematic literature search was conducted in PubMed, Embase, Web of Science, and Cochrane databases to identify studies pertaining to freehand EVD placement through March 30, 2022. Studies were included if they reported percentage of EVDs placed successfully on the first pass attempt, or final catheter location as defined by the Kakarla Grading System. Pooled weighted incidence estimates and 95% confidence intervals (95%CI) were calculated using a random effects model. RESULTS: Of the 2964 results returned from the literature search, 39 studies were included in this meta-analysis. These studies reported on 6313 EVDs placed via freehand technique in 6070 patients with the following respective incidence: successful EVD placement on the first attempt (78%, 95%CI: 67-86%); placement with a Kakarla Grade of 1 (optimal location) (72%, 95%CI: 66-77%); hemorrhage (7%, 95%CI: 6-10%), and infection (5%, 95%CI: 3-8%). CONCLUSIONS: Only 78% of EVDs in this meta-analysis were placed successfully on the first pass, and only 72% of final placements were deemed optimal. This represents a relatively high rate of suboptimal outcomes with respect to EVD placement, which could potentially be avoided with the use of navigation-assisted placement techniques.

Optimizing Choice and Timing of Behavioral Outcome Tests After Repetitive Mild Traumatic Brain Injury: A Machine Learning-Based Approach on Multiple Pre-Clinical Experiments.

Repetitive mild traumatic brain injury (rmTBI) is a potentially debilitating condition with long-term sequelae. Animal models are used to study rmTBI in a controlled environment, but there is currently no established standard battery of behavioral tests used. Primarily, we aimed to identify the best combination and timing of behavioral tests to distinguish injured from uninjured animals in rmTBI studies, and secondarily, to determine whether combinations of independent experiments have better behavioral outcome prediction accuracy than individual experiments. Data from 1203 mice from 58 rmTBI experiments, some of which have already been published, were used. In total, 11 types of behavioral tests were measured by 37 parameters at 13 time points during the first 6 months after injury. Univariate regression analyses were used to identify optimal combinations of behavioral tests and whether the inclusion of multiple heterogenous experiments improved accuracy. k-means clustering was used to determine whether a combination of multiple tests could distinguish mice with rmTBI from uninjured mice. We found that a combination of behavioral tests outperformed individual tests alone when distinguishing animals with rmTBI from uninjured animals. The best timing for most individual behavioral tests was 3-4 months after first injury. Overall, Morris water maze (MWM; hidden and probe frequency) was the behavioral test with the best capability of detecting injury effects (area under the curve [AUC] = 0.98). Combinations of open field tests and elevated plus mazes also performed well (AUC = 0.92), as did the forced swim test alone (AUC = 0.90). In summary, multiple heterogeneous experiments tended to predict outcome better than individual experiments, and MWM 3-4 months after injury was the optimal test, also several combinations also performed well. In order to design future pre-clinical rmTBI trials, we have included an interactive application available online utilizing the data from the study via the Supplementary URL.

The Impact of Tort Reforms on the Neurosurgical Malpractice Environment: A Systematic Review of Literature.

BACKGROUND: Neurosurgeons, especially spine surgeons, have the highest risk of facing a malpractice claim. Average verdicts in spine surgery litigation has been shown to be over USD $1 million/case. This systematic review aimed to clarify the impact of tort reforms on neurosurgical health care environments across the United States, including patient outcomes, practice of defensive medicine, and physician supply aims. METHODS: A systematic literature search was performed using PubMed, Embase, Cochrane, and Web of Science databases until May 13, 2022. Study quality was assessed using the quality assessment tool for studies reporting prevalence data. RESULTS: Five studies (all rated as good quality) were included. Two studies found that in higher-risk state malpractice environments, risk of postoperative complications was higher and odds of nonhome discharge were larger (odds ratio 1.1169, 95% confidence interval 1.139-1.200). One study found that neurosurgeons reported practice of defensive medicine by ordering more imaging in a higher-risk environment, while this was not shown in a study examining imaging rates in different medicolegal environments. One study observed that noneconomic damage caps were associated with a 3.9% increase of physician supply in high-risk specialties. CONCLUSIONS: There was a suggestive association between tort reforms and less practice of defensive medicine among neurosurgeons, improvement in postoperative outcomes in spinal fusion patients, and increase in physician supply. More elaborate studies on the medicolegal environment in neurosurgical practice are needed to give more insight on the current size of the problem that litigation presents in the United States and the effects tort reforms have on neurosurgical health care environments.

Long-term health-related quality of life after trauma with and without traumatic brain injury: a prospective cohort study.

To purpose was to assess and compare the health-related quality of life (HRQoL) and risk of depression two years after trauma, between patients with and without traumatic brain injury (TBI) in a mixed Swedish trauma cohort. In this prospective cohort study, TBI and non-TBI trauma patients included in the Swedish Trauma registry 2019 at a level II trauma center in Stockholm, Sweden, were contacted two years after admission. HRQoL was assessed with RAND-36 and EQ-5D-3L, and depression with Montgomery Åsberg depression Rating Scale self-report (MADRS-S). Abbreviated Injury Score (AIS) head was used to grade TBI severity, and American Society of Anesthesiologists (ASA) score was used to assess comorbidities. Data were compared using Chi-squared test, Mann Whitney U test and ordered logistic regression, and Bonferroni correction was applied. A total of 170 of 737 eligible patients were included. TBI was associated with higher scores in 5/8 domains of RAND-36 and 3/5 domains of EQ-5D (p < 0.05). No significant difference in MADRS-S. An AIS (head) of three or higher was associated with lower scores in five domains of RAND-36 and two domains of EQ-5D but not for MADRS-S. An ASA-score of three was associated with lower scores in all domains of both RAND-36 (p < 0.05, except mental health) and EQ-5D (p < 0.001, except anxiety/depression), but not for MADRS-S. In conclusion, patients without TBI reported a lower HRQoL than TBI patients two years after trauma. TBI severity assessed according to AIS (head) was associated with HRQoL, and ASA-score was found to be a predictor of HRQoL, emphasizing the importance of considering pre-injury health status when assessing outcomes in TBI patients.

Stockholm score of lesion detection on computed tomography following mild traumatic brain injury (SELECT-TBI): study protocol for a multicentre, retrospective, observational cohort study.

INTRODUCTION: Mild traumatic brain injury (mTBI) is one of the most common reasons for emergency department (ED) visits. A portion of patients with mTBI will develop an intracranial lesion that might require medical or surgical intervention. In these patients, swift diagnosis and management is paramount. Several guidelines have been developed to help direct patients with mTBI for head CT scanning, but they lack specificity, do not consider the interactions between risk factors and do not provide an individualised estimate of intracranial lesion risk. The aim of this study is to create a model that estimates individualised intracranial lesion risks in patients with mTBI who present to the ED. METHODS AND ANALYSIS: This will be a retrospective cohort study conducted at ED hospitals in Stockholm, Sweden. Eligible patients are adults (≥15 years) with mTBI who presented to the ED within 24 hours of injury and performed a CT scan. The primary outcome will be a traumatic lesion on head CT. The secondary outcomes will be any clinically significant lesion, defined as an intracranial finding that led to neurosurgical intervention, hospital admission ≥48 hours due to TBI or death due to TBI. Machine-learning models will be applied to create scores predicting the primary and secondary outcomes. An estimated 20 000 patients will be included. ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority (Dnr: 2020-05728). The research findings will be disseminated through peer-reviewed scientific publications and presentations at international conferences. TRIAL REGISTRATION NUMBER: NCT04995068.

Surgical outcomes of pediatric brain tumors in Sub-Saharan Africa: A systematic review.

Background: Pediatric Brain Tumors (PBT) are a common cause of cancer-related mortality globally. Contrary to high-income countries (HIC), survival rates in low-and-middle income countries (LMIC) remains low despite advances in neurosurgical care and diagnostics over the past decades. The aim of this systematic review was to investigate the surgical outcomes for PBT in Sub-Saharan Africa, and the distribution of PBT types. Methods: A systematic review was conducted on PubMed, for all available literature on the surgical outcomes of PBT in Sub-Saharan Africa, published before May 3, 2022. Two reviewers performed abstract, full text screening and data collection independently, resolving any conflicts by consensus. Results: The search yielded 256 studies, of which 22 met the inclusion criteria, amounting to a total of 243 patients. Nigeria was the country with most data. Only subgroups of patients could be extracted from 12 studies, and variables of interest in 6 studies had inconsistent sample sizes. The age centered around 9 years, and there were approximately equal number of girls and boys. The most common tumor was medulloblastoma, followed by craniopharyngioma and astrocytoma. There was large heterogeneity in the reporting of outcomes, and a trend was difficult to discern, considering the large number of different tumor types and different extents of resection. Discussion and conclusion: Data is insufficient and inconsistent, precluding statistical conclusions. There is a need for more studies in the field.

A national stratification of the global macroeconomic burden of central nervous system cancer.

OBJECTIVE: Country-by-country estimates of the macroeconomic disease burden of central nervous system (CNS) cancers are important when determining the allocation of resources related to neuro-oncology. Accordingly, in this study the authors investigated macroeconomic losses related to CNS cancer in 173 countries and identified pertinent epidemiological trends. METHODS: Data for CNS cancer incidence, mortality, and disability-adjusted life years (DALYs) were collected from the Global Burden of Disease 2019 database. Gross domestic product data were combined with DALY data to estimate economic losses using a value of lost welfare approach. RESULTS: The mortality-to-incidence ratio of CNS cancer in 2019 was 0.60 in high-income regions compared to 0.82 in Sub-Saharan Africa and 0.87 in Central Europe, Eastern Europe, and Central Asia. Welfare losses varied across both high- and low-income countries. Welfare losses attributable to CNS cancer in Japan represented 0.07% of the gross domestic product compared to 0.23% in Germany. In low- and middle-income countries, Iraq reported welfare losses of 0.20% compared to 0.04% in Angola. Globally, the DALY rate in 2019 was the same for CNS cancer as for prostate cancer at 112 per 100,000 person-years, despite a 75% lower incidence rate, equating to CNS cancer welfare losses of 182 billion US dollars. CONCLUSIONS: Macroeconomic losses vary across high- and low-income settings and appear to be region specific. These differences may be explained by differences in regional access to screening and diagnosis, population-level genetic predispositions, and environmental risk factors. Mortality-to-incidence ratios are higher in low- and middle-income countries than in high-income countries, highlighting possible gaps in treatment access. Quantification of macroeconomic losses related to CNS cancer can help to justify the spending of finite resources to improve outcomes for neuro-oncological patients globally.

The cerebrospinal fluid proteome of preterm infants predicts neurodevelopmental outcome.

Background: Survival rate increases for preterm infants, but long-term neurodevelopmental outcome predictors are lacking. Our primary aim was to determine whether a specific proteomic profile in cerebrospinal fluid (CSF) of preterm infants differs from that of term infants and to identify novel biomarkers of neurodevelopmental outcome in preterm infants. Methods: Twenty-seven preterm infants with median gestational age 27 w + 4 d and ten full-term infants were enrolled prospectively. Protein profiling of CSF were performed utilizing an antibody suspension bead array. The relative levels of 178 unique brain derived proteins and inflammatory mediators, selected from the Human Protein Atlas, were measured. Results: The CSF protein profile of preterm infants differed from that of term infants. Increased levels of brain specific proteins that are associated with neurodevelopment and neuroinflammatory pathways made up a distinct protein profile in the preterm infants. The most significant differences were seen in proteins involved in neurodevelopmental regulation and synaptic plasticity, as well as components of the innate immune system. Several proteins correlated with favorable outcome in preterm infants at 18-24 months corrected age. Among the proteins that provided strong predictors of outcome were vascular endothelial growth factor C, Neurocan core protein and seizure protein 6, all highly important in normal brain development. Conclusion: Our data suggest a vulnerability of the preterm brain to postnatal events and that alterations in protein levels may contribute to unfavorable neurodevelopmental outcome.

Telemedicine and the right to health: A neurosurgical perspective.

Neurosurgical task force is limited and unevenly distributed. Telemedicine has become increasingly popular, and could help neurosurgical centers meet patient right to care. This scoping review aims to evaluate the impact and feasibility of telemedicine on the right to neurosurgical care, using the AAAQ toolbox. The AAAQ toolbox consists of Availability, Accessibility, Acceptability and Quality. Neurosurgical availability is limited by the number of neurosurgeons, but by using task shifting and -sharing via telemedicine, the number of patients receiving neurosurgical care could increase without increasing the number of neurosurgeons. Telemedicine can improve geographic accessibility to neurosurgical care, but may also introduce technological literacy barriers. Acceptability of telemedicine is a double-edged sword; while a useful service, telemedicine also creates ethical concerns regarding privacy and confidentiality. Regulations and adaptations for vulnerable patient groups are key considerations for deploying telemedicine. Finally, there is emerging evidence that the quality of remote neurosurgical diagnostics and care can keep high standards. Overall, telemedicine has the potential of taking neurosurgery one step closer to meeting patient right to health, globally.

Proteomic profiles in cerebrospinal fluid predicted death and disability in term infants with perinatal asphyxia: A pilot study.

AIM: Perinatal asphyxia, resulting in hypoxic-ischaemic encephalopathy (HIE), has been associated with high mortality rates and severe lifelong neurodevelopmental disabilities. Our aim was to study the association between the proteomic profile in cerebrospinal fluid (CSF) and the degree of HIE and long-term outcomes. METHODS: We prospectively enrolled 18-term born infants with HIE and 10-term born controls between 2000 and 2004 from the Karolinska University Hospital. An antibody suspension bead array and FlexMap3D analysis was used to characterise 178 unique brain-derived and inflammation associated proteins in their CSF. RESULTS: Increased CSF concentrations of several brain-specific proteins were observed in the proteome of HIE patients compared with the controls. An upregulation of neuroinflammatory pathways was also noted and this was confirmed by pathway analysis. Principal component analysis revealed a gradient from favourable to unfavourable HIE grades and outcomes. The proteins that provided strong predictors were structural proteins, including myelin basic protein and alpha-II spectrin. The functional proteins included energy-related proteins like neuron-specific enolase and synaptic regulatory proteins. Increased CSF levels of 51 proteins correlated with adverse outcomes in infants with HIE. CONCLUSION: Brain-specific proteins and neuroinflammatory mediators in CSF may predict HIE degrees and outcomes after perinatal asphyxia.

Systemic inflammation alters the neuroinflammatory response: a prospective clinical trial in traumatic brain injury.

BACKGROUND: Neuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development; however, how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition. METHODS: TBI patients recruited to a previous randomised controlled trial studying the effects of the drug anakinra (Kineret®), a human recombinant interleukin-1 receptor antagonist (rhIL1ra), were used (n = 10 treatment arm, n = 10 control arm). Cytokine concentrations were measured in arterial and jugular venous samples twice a day, as well as in microdialysis-extracted brain extracellular fluid (ECF) following pooling every 6 h. C-reactive protein level (CRP), white blood cell count (WBC), temperature and confirmed systemic clinical infection were used as systemic markers of inflammation. Principal component analyses, linear mixed-effect models, cross-correlations and multiple factor analyses were used. RESULTS: Jugular and arterial blood held similar cytokine information content, but brain-ECF was markedly different. No clear arterial to jugular gradient could be seen. No substantial delayed temporal associations between blood and brain compartments were detected. The development of a systemic clinical infection resulted in a significant decrease of IL1-ra, G-CSF, PDGF-ABBB, MIP-1b and RANTES (p < 0.05, respectively) in brain-ECF, even if adjusting for injury severity and demographic factors, while an increase in several cytokines could be seen in arterial blood. CONCLUSIONS: Systemic inflammation, and infection in particular, alters cytokine levels with different patterns seen in brain and in blood. Cerebral inflammatory monitoring provides independent information from arterial and jugular samples, which both demonstrate similar information content. These findings could present potential new treatment options in severe TBI patients, but novel prospective trials are warranted to confirm these associations.