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The COVID-19 pandemic response has been hindered by the absence of an efficient antiviral therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The reason why the previous preventative approach to COVID-19 solely through vaccines has failed could be a lack of understanding of how quickly the SARS-CoV-2 virus evolves. Given the absence of specific treatments for the virus, efforts have been underway to explore treatment options. Drug repurposing involves identifying new therapeutic uses for approved drugs, proving to be a time-saving strategy with minimal risk of failure. In this study, we report the successful use of a multidrug approach in patients with COVID-19. Successful administration of multidrug therapy, such as combinations of hydroxychloroquine and azithromycin, doxycycline and ivermectin, or ivermectin, doxycycline, and azithromycin, has been reported. Multidrug therapy is effective because of the differing mechanisms of action of these drugs, and it may also mitigate the emergence of drug-resistant SARS-CoV-2 strains. The medicines were lopinavir/ritonavir (Kaletra), bamlanivimab (monoclonal antibody), glycopyrrolate-formoterol (Bevespi), ciclesonide (Alvesco), famotidine (Pepcid), and diphenhydramine (Benadryl).

Background: Traumatic spinal injury (TSI) is a disease of significant global health burden, particularly in low and middle-income countries where road traffic-related trauma is increasing. This study compared the demographics, injury patterns, and outcomes of TSI caused by road traffic accidents (RTAs) to non-traffic related TSI., Methods: A retrospective analysis was conducted using a neurotrauma registry from the Muhimbili Orthopaedic Institute (MOI) in Tanzania, a national referral center for spinal injuries. Patient sociodemographic characteristics, injury level, and severity were compared across mechanisms of injury. Neurological improvement, neurological deterioration, and mortality were compared between those sustaining TSI through an RTA versus non-RTA, using univariable and multivariable analyses., Results: A total of 626 patients were included, of which 302 (48%) were RTA-related. The median age was 34 years, and 532 (85%) were male. RTAs had a lower male preponderance compared to non-RTA causes (238/302, 79% vs. 294/324, 91%, p<0.001) and a higher proportion of cervical injuries (144/302, 48% vs. 122/324, 38%, p<0.001). No significant differences between RTA and non-RTA mechanisms were found in injury severity, time to admission, length of hospital stay, surgical intervention, neurological outcomes, or in-hospital mortality. Improved neurological outcomes were associated with incomplete injuries (AIS B-D), while higher mortality rates were linked to cervical injuries and complete (AIS A) injuries., Conclusion: Our study in urban Tanzania finds no significant differences in outcomes between spinal injuries from road traffic accidents (RTAs) and non-RTA causes, suggesting the need for equitable resource allocation in spine trauma programs. Highlighting the critical link between cervical injuries and increased mortality, our findings call for targeted interventions across all causes of traumatic spinal injuries (TSI). We advocate for a comprehensive trauma care system that merges efficient pre-hospital care, specialized treatment, and prevention measures, aiming to enhance outcomes and ensure equity in trauma care in low- and middle-income countries., Competing Interests: The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Scott L. Zuckerman is a consultant for the National Football League and Medtronic. Roger Hartl is a DePuy Synthes and Brainlab consultant and has royalties from Zimmer Biomet. He is also an advisor for 3D Bio and Real Spine. No other author declares any financial interests or personal relationships., (Copyright: © 2024 Ikwuegbuenyi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Esports gambling has steadily grown in popularity alongside esports itself. While research has been increasing in the field of esports-related gambling, no study has yet reviewed the relevant literature on esports gambling. The present study aimed to comprehensively review all empirical research conducted in the wider field of esports gambling. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was undertaken using PsycINFO, PubMed, Scopus, and Web of Science databases. Only empirical studies were included and were also assessed for potential biases using the ROBUST guidelines. A total of 30 studies from eight countries were included in the review. Esports gamblers were found more likely to be young males, likely to score high on problematic gambling scales, and likely to belong to households speaking a non-English language at home in English speaking countries. Esports gamblers are a unique type of gambling population, with rare characteristics and behaviors compared to other types of gamblers. Given the limited number of studies, there is a need for further research in this field to understand these populations, as well as the need for longitudinal research., (© 2023. The Author(s).)

Prehospital care markedly influences outcome from traumatic brain injury, yet it remains highly variable. The Brain Trauma Foundation's guidelines informing prehospital care, first published in 2002, have sought to identify and disseminate best practices. Many of its recommendations relate to the management of airway, breathing and circulation, and infrastructure for this care. Compliance with the second edition of these guidelines has been associated with significantly improved survival. A working group developed evidence-based recommendations informing assessment, treatment, and transport decision-making relevant to the prehospital care of brain injured patients. A literature search spanning May 2005 to January 2022 supplemented data contained in the 2nd edition. Identified studies were assessed for quality and used to inform evidence-based recommendations. A total of 122 published articles formed the evidentiary base for this guideline update including 5 providing Class I evidence, 35 providing Class II evidence, and 98 providing Class III evidence for the various topics. Forty evidence-based recommendations were generated, 30 of which were strong and 10 of which were weak. In many cases, new evidence allowed guidelines from the 2nd edition to be strengthened. Development of guidelines on some new topics was possible including the prehospital administration of tranexamic acid. A management algorithm is also presented. These guidelines help to identify best practices for prehospital traumatic brain injury care, and they also identify gaps in knowledge which we hope will be addressed before the next edition., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Background: Postgraduate neurosurgical training is essential to develop a neurosurgical workforce with the skills and knowledge to address patient needs for neurosurgical care. In Tanzania, the number of neurosurgeons and neurosurgical services offered have expanded in the past 40 years. Training opportunities within the country, however, are not sufficient to meet the needs of residents, specialists, and nurses in neurosurgery, forcing many to train outside the country incurring associated costs and burdens. We report on the Dar es Salaam Global Neurosurgery Course, which aims to provide local training to neurosurgical health care providers in Tanzania and surrounding countries., Methods: We report the experience of the Global Neurosurgery Course held in March 2023 in Dar es Salaam, Tanzania. We describe the funding, planning, organization, and teaching methods along with participant and faculty feedback., Results: The course trained 121 participants with 63 faculty-42 from Tanzania and 21 international faculty. Training methods included lectures, hands-on surgical teaching, webinars, case discussions, surgical simulation, virtual reality, and bedside teaching. Although there were challenges with equipment and Internet connectivity, participant feedback was positive, with overall improvement in knowledge reported in all topics taught during the course., Conclusions: International collaboration can be successful in delivering topic-specific training that aims to address the everyday needs of surgeons in their local setting. Suggestions for future courses include increasing training on allied topics to neurosurgery and neurosurgical subspecialty topics, reflecting the growth in neurosurgical capacity and services offered in Tanzania., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Quality health care in low and middle-income countries (LMICs) is constrained by financing of care., Research Question: What is the effect of ability to pay on critical care management of patients with severe traumatic brain injury (sTBI)?, Material and Methods: Data on sTBI patients admitted to a tertiary referral hospital in Dar-es-Salaam, Tanzania, were collected between 2016 and 2018, and included payor mechanisms for hospitalization costs. Patients were grouped as those who could afford care and those who were unable to pay., Results: Sixty-seven patients with sTBI were included. Of those enrolled, 44 (65.7%) were able to pay and 15 (22.3%) were unable to pay costs of care upfront. Eight (11.9%) patients did not have a documented source of payment (unknown identity or excluded from further analysis). Overall mechanical ventilation rates were 81% (n=36) in the affordable group and 100% (n=15) in the unaffordable group (p=0.08). Computed tomography (CT) rates were 71.6% (n=48) overall, 100% (n=44) and 0% respectively (p<0.01); Surgical rates were 16.4% (n=11) overall, 18.2% (n=8) vs. 13.3% (n=2) (p=0.67) respectively. Two-week mortality was 59.7% overall (n=40), 47.7% (n=21) in the affordable group and 73.3% (n=11) in the unaffordable group (p=0.09) (adjusted OR 0.4; 95% CI: 0.07-2.41, p=0.32)., Discussion and Conclusion: Ability to pay appears to have a strong association with the use of head CT and a weak association with mechanical ventilation in the management of sTBI. Inability to pay increases redundant or sub-optimal care, and imposes a financial burden on patients and their relatives., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The present paper provides an overview of the possible risks, harms, and challenges that might arise with the development of the esports field and pose a threat to professional esports players, spectators, bettors and videogame players, including underage players. These include physical and mental health issues, gambling and gambling-like elements associated with videogames and esports, the challenges arising from pursuing a career in esports, the unique difficulties women face, and a need for supporting professional esports players. It briefly discusses possible responses and suggestions regarding how to address and mitigate these negative consequences. It emphasizes the need for cooperation and collaboration between various stakeholders: researchers, policymakers, regulators, the gaming industry, esports organizations, healthcare and treatment providers, educational institutes and the need for further evidence-based information.

Introduction: The Muhimbili Orthopaedic Institute in collaboration with Weill Cornell Medicine organises an annual neurosurgery training course in Dar es Salaam, Tanzania. The course teaches theory and practical skills in neurotrauma, neurosurgery, and neurointensive care to attendees from across Tanzania and East Africa. This is the only neurosurgical course in Tanzania, where there are few neurosurgeons and limited access to neurosurgical care and equipment., Research Question: To investigate the change in self-reported knowledge and confidence in neurosurgical topics amongst the 2022 course attendees., Material and Methods: Course participants completed pre and post course questionnaires about their background and self-rated their knowledge and confidence in neurosurgical topics on a five point scale from one (poor) to five (excellent). Responses after the course were compared with those before the course., Results: Four hundred and seventy participants registered for the course, of whom 395(84%) practiced in Tanzania. Experience ranged from students and newly qualified professionals to nurses with more than 10 years of experience and specialist doctors. Both doctors and nurses reported improved knowledge and confidence across all neurosurgical topics following the course. Topics with lower self-ratings prior to the course showed greater improvement. These included neurovascular, neuro-oncology, and minimally invasive spine surgery topics. Suggestions for improvement were mostly related to logistics and course delivery rather than content., Discussion and Conclusion: The course reached a wide range of health care professionals in the region and improved neurosurgical knowledge, which should benefit patient care in this underserved region., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ibrahim Hussain reports a relationship with 3DBio that includes: consulting or advisory. Ibrahim Hussain reports a relationship with AO Spine that includes: consulting or advisory. Ibrahim Hussain reports a relationship with AO Spine that includes: funding grants. Fabian Sommer reports a relationship with Baxter that includes: speaking and lecture fees. Roger Hartl reports a relationship with DePuy Synthes that includes: consulting or advisory. Roger Hartl reports a relationship with Brainlab AG that includes: consulting or advisory. Roger Hartl reports a relationship with Ulrich that includes: consulting or advisory. Roger Hartl reports a relationship with Zimmer Biomet that includes: equity or stocks. Roger Hartl reports a relationship with RealSpine that includes: equity or stocks., (© 2023 The Authors.)

Vaccine development against COVID-19 has mitigated severe disease. However, reports of rare but serious adverse events following immunization (sAEFI) in the young populations are fuelling parental anxiety and vaccine hesitancy. With a very early season of viral illnesses including COVID-19, respiratory syncytial virus (RSV), influenza, metapneumovirus and several others, children are facing a winter with significant respiratory illness burdens. Yet, COVID-19 vaccine and booster uptake remain sluggish due to the mistaken beliefs that children have low rates of severe COVID-19 illness as well as rare but severe complications from COVID-19 vaccine are common. In this study we examined composite sAEFI reported in association with COVID-19 vaccines in the United States (US) amongst 5-17-year-old children, to ascertain the composite reported risk associated with vaccination. Between December 13, 2020, and April 13, 2022, a total of 467,890,599 COVID-19 vaccine doses were administered to individuals aged 5-65 years in the US, of which 180 million people received at least 2 doses. In association with these, a total of 177,679 AEFI were reported to the Vaccine Adverse Event reporting System (VAERS) of which 31,797 (17.9%) were serious. The rates of ED visits per 100,000 recipients were 2.56 (95% CI: 2.70-3.47) amongst 5-11-year-olds, 18.25 (17.57-18.95) amongst 12-17-year-olds and 33.74 (33.36-34.13) amongst 18-65-year olds; hospitalizations were 1.07 (95% CI 0.87-1.32) per 100,000 in 5-11-year-olds, 6.83 (6.42-7.26) in 12-17-year olds and 8.15 (7.96-8.35) in 18-65 years; life-threatening events were 0.14 (95% CI: 0.08-0.25) per 100,000 in 5-11-year olds, 1.22 (1.05-1.41) in 12-17-year-olds and 2.96 (2.85-3.08) in 18-65 year olds; and death 0.03 (95% CI 0.01-0.10) per 100,000 in 5-11 year olds, 0.08 (0.05-0.14) amongst 12-17-year olds and 0.76 (0.71-0.82) in 18-65 years age group. The results of our study from national population surveillance data demonstrate rates of reported serious AEFIs amongst 5-17-year-olds which appear to be significantly lower than in 18-65-year-olds. These low risks must be taken into account in overall recommendation of COVID-19 vaccination amongst children., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mangat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The burden of spinal trauma in low- and middle-income countries (LMICs) is immense, and its management is made complex in such resource-restricted settings. Algorithmic evidence-based management is cost-prohibitive, especially with respect to spinal implants, while perioperative care is work-intensive, making overall care dependent on multiple constraints. The objective of this study was to identify determinants of decision-making for surgical intervention, improvement in function, and in-hospital mortality among patients experiencing acute spinal trauma in resource-constrained settings., Methods: This study was a retrospective analysis of prospectively collected data in a cohort of patients with spinal trauma admitted to a tertiary referral hospital center in Dar es Salam, Tanzania. Data on demographic, clinical, and treatment characteristics were collected as part of a quality improvement neurotrauma registry. Outcome measures were surgical intervention, American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade improvement, and in-hospital mortality, based on existing treatment protocols. Univariate analyses of demographic and clinical characteristics were performed for each outcome of interest. Using the variables associated with each outcome, a machine learning algorithm-based regression nonparametric decision tree model utilizing a bootstrapping method was created and the accuracy of the three models was estimated., Results: Two hundred eighty-four consecutively admitted patients with acute spinal trauma were included over a period of 33 months. The median age was 34 (IQR 26-43) years, 83.8% were male, and 50.7% had experienced injury in a motor vehicle accident. The median time to hospital admission after injury was 2 (IQR 1-6) days; surgery was performed after a further median delay of 22 (IQR 13-39) days. Cervical spine injury comprised 38.4% of the injuries. Admission AIS grades were A in 48.9%, B in 16.2%, C in 8.5%, D in 9.5%, and E in 16.6%. Nearly half (45.1%) of the patients underwent surgery, 12% had at least one functional improvement in AIS grade, and 11.6% died in the hospital. Determinants of surgical intervention were age ≤ 30 years, spinal injury level, admission AIS grade, delay in arrival to the referral hospital, undergoing MRI, and type of insurance; admission AIS grade, delay to arrival to the hospital, and injury level for functional improvement; and delay to arrival, injury level, delay to surgery, and admission AIS grade for in-hospital mortality. The best accuracies for the decision tree models were 0.62, 0.34, and 0.93 for surgery, AIS grade improvement, and in-hospital mortality, respectively., Conclusions: Operative intervention and functional improvement after acute spinal trauma in this tertiary referral hospital in an LMIC environment were low and inconsistent, which suggests that nonclinical factors exist within complex resource-driven decision-making frameworks. These nonclinical factors are highlighted by the authors' results showing clinical outcomes and in-hospital mortality were determined by natural history, as evidenced by the highest accuracy of the model predicting in-hospital mortality.

Neurotrauma surveillance data on burden and severity of disease serves as a tool to define legislations, guide high-yield risk-specific prevention, and evaluate and monitor management strategies for adequate resource allocation. In this scoping review, Barthélemy and colleagues demonstrate the gap in neurotrauma surveillance in low- and middle-income countries (LMICs) and suggest strategies for governance in neurotrauma surveillance. We underline state accountability as well as the need for the close integration of academic and tertiary care clinical practitioners and policy-makers in addressing the public health crisis caused by neurotrauma. Additionally, multiple sources for surveillance must be included, especially in communities where victims may remain without access to formal healthcare. Finally, we offer insights into possible ways of increasing the visibility of neurotrauma on political agendas., (© 2023 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Objective: To analyze rates of reported severe adverse events after immunization (sAEFI) attributed to SARS-CoV-2 vaccines in the United States (US) using safety surveillance data., Methods: Observational study of sAEFI reported to the vaccine adverse events reporting system (VAERS) between December 13, 2020, to December 13, 2021, and attributed to SARS-CoV-2 vaccination programs across all US states and territories. All sAEFI in conjunction with mRNA (BNT-162b2 or mRNA-1273) or adenovector (Ad26.COV2.S) vaccines were included. The 28-day crude cumulative rates for reported emergency department (ED) visits and sAEFI viz. hospitalizations, life-threatening events and deaths following SARS-CoV-2 vaccination were calculated. Incidence rate ratios (IRRs) of reported sAEFI were compared between mRNA and adenovector vaccines using generalized Poisson regression models., Results: During the study period, 485 million SARS-CoV-2 vaccines doses were administered nationwide, and 88,626 sAEFI reported in VAERS. The 28-day crude cumulative reporting rates per 100,000 doses were 14.97 (95% confidence interval, 14.86-18.38) for ED visits, 5.32 (5.26-5.39) for hospitalizations, 1.72 (1.68-1.76) for life-threatening events, and 1.08 (1.05-1.11) for deaths. Females had two-fold rates for any reported AEFI compared to males, but lower adjusted IRRs for sAEFI. Cumulative rates per dose for reported sAEFI attributed to adenovector vaccine were 2-3-fold higher, and adjusted IRRs 1.5-fold higher than mRNA vaccines., Conclusions: Overall cumulative rates for reported sAEFI following SARS-CoV-2 vaccination in the US over 1 year were very low; single-dose adenovector vaccine had 1.5-fold higher adjusted rates for reported sAEFI, which may however equate with multiple-doses mRNA vaccine regimens. These data indicate absence of high risks of sAEFI following SARS-CoV-2 vaccines and support safety equipoise between mRNA and adenovector vaccines. Public health messaging of these data is critical to overcome heuristic biases. Furthermore, these data may support ongoing adenovector vaccine use, especially in low- and middle-income countries due to affordability, logistical and cold chain challenges., Competing Interests: Author AB was employed by the company Transmissible BV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mangat, Musah, Luedtke, Syed, Maramattom, Maruthanal, Bosman and Kostkova.)

Acute neurologic illnesses (ANI) contribute significantly to the global burden of disease and cause disproportionate death and disability in low-income and middle-income countries (LMICs) where neurocritical care resources and expertise are limited. Shifting epidemiologic trends in recent decades have increased the worldwide burden of noncommunicable diseases, including cerebrovascular disease and traumatic brain injury, which coexist in many LMICs with a persistently high burden of central nervous system infections such as tuberculosis, neurocysticercosis, and HIV-related opportunistic infections and complications. In the face of this heavy disease burden, many resource-limited countries lack the infrastructure to provide adequate care for patients with ANI. Major gaps exist between wealthy and poor countries in access to essential resources such as intensive care unit beds, neuroimaging, clinical laboratories, neurosurgical capacity, and medications for managing complex neurologic emergencies. Moreover, many resource-limited countries face critical shortages in health care workers trained to manage neurologic emergencies, with subspecialized neurocritical care expertise largely absent outside of high-income countries. Numerous opportunities exist to overcome these challenges through capacity-building efforts that improve outcomes for patients with ANI in resource-limited countries. These include research on needs and best practices for ANI management in LMICs, developing systems for effective triage, education and training to expand the neurology workforce, and supporting increased collaboration and data sharing among LMIC health care workers and systems. The success of these efforts in curbing the disproportionate and rising impact of ANI in LMICs will depend on the coordinated engagement of the global neurocritical care community., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: We present an exploratory analysis of the occurrence of early corticothalamic connectivity disruption after aneurysmal subarachnoid hemorrhage (SAH) and its correlation with clinical outcomes., Methods: We conducted a retrospective study of patients with acute SAH who underwent continuous electroencephalography (EEG) for impairment of consciousness. Only patients undergoing endovascular aneurysm treatment were included. Continuous EEG tracings were reviewed to obtain artifact-free segments. Power spectral analyses were performed, and segments were classified as A (only delta power), B (predominant delta and theta), C (predominant theta and beta), or D (predominant alpha and beta). Each incremental category from A to D implies greater preservation of corticothalamic connectivity. We dichotomized categories as AB for poor connectivity and CD for good connectivity. The modified Rankin Scale score at follow-up and in-hospital mortality were used as outcome measures., Results: Sixty-nine patients were included, of whom 58 had good quality EEG segments for classification: 28 were AB and 30 were CD. Hunt and Hess and World Federation of Neurological Surgeons grades were higher and the initial Glasgow Coma Scale score was lower in the AB group compared with the CD group. AB classification was associated with an adjusted odds ratio of 5.71 (95% confidence interval 1.61-20.30; p < 0.01) for poor outcome (modified Rankin Scale score 4-6) at a median follow-up of 4 months (interquartile range 2-6) and an odds ratio of 5.6 (95% confidence interval 0.98-31.95; p = 0.03) for in-hospital mortality, compared with CD., Conclusions: EEG spectral-power-based classification demonstrates early corticothalamic connectivity disruption following aneurysmal SAH and may be a mechanism involved in early brain injury. Furthermore, the extent of this disruption appears to be associated with functional outcome and in-hospital mortality in patients with aneurysmal SAH and appears to be a potentially useful predictive tool that must be validated prospectively., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Coagulopathy in traumatic brain injury (TBI) occurs frequently and is associated with poor outcomes. Conventional coagulation assays (CCA) traditionally used to diagnose coagulopathy are often not time sensitive and do not assess complete hemostatic function. Viscoelastic hemostatic assays (VHAs) including thromboelastography and rotational thromboelastography provide a useful rapid and comprehensive point-of-care alternative for identifying coagulopathy, which is of significant consequence in patients with TBI with intracranial hemorrhage., Methods: A systematic review was performed in accordance with PRISMA guidelines to identify studies comparing VHA with CCA in adult patients with TBI. The following differences in outcomes were assessed based on ability to diagnose coagulopathy: mortality, need for neurosurgical intervention, and progression of traumatic intracranial hemorrhage (tICH)., Results: Abnormal reaction time (R time), maximum amplitude, and K value were associated with increased mortality in certain studies but not all studies. This association was reflected across studies using different statistical parameters with different outcome definitions. An abnormal R time was the only VHA parameter found to be associated with the need for neurosurgical intervention in 1 study. An abnormal R time was also the only VHA parameter associated with progression of tICH. Overall, many studies also reported abnormal CCAs, mainly activated partial thromboplastin time, to be associated with poor outcomes., Conclusions: Given the heterogenous nature of the available evidence including methodology and study outcomes, the comparative difference between VHA and CCA in predicting rates of neurosurgical intervention, tICH progression, or mortality in patients with TBI remains inconclusive., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Study Design: Retrospective cost-effectiveness analysis., Objectives: While the incidence of traumatic spine injury (TSI) is high in low-middle income countries (LMICs), surgery is rarely possible due to cost-prohibitive implants. The objective of this study was to conduct a preliminary cost-effectiveness analysis of operative treatment of TSI patients in a LMIC setting., Methods: At a tertiary hospital in Tanzania from September 2016 to May 2019, a retrospective analysis was conducted to estimate the cost-effectiveness of operative versus nonoperative treatment of TSI. Operative treatment included decompression/stabilization. Nonoperative treatment meant 3 months of bed rest. Direct costs included imaging, operating fees, surgical implants, and length of stay. Four patient scenarios were chosen to represent the heterogeneity of spine trauma: Quadriplegic, paraplegic, neurologic improvement, and neurologically intact. Disability-adjusted-life-years (DALYs) and incremental-cost-effectiveness ratios were calculated to determine the cost per unit benefit of operative versus nonoperative treatment. Cost/DALY averted was the primary outcome (i.e., the amount of money required to avoid losing 1 year of healthy life)., Results: A total of 270 TSI patients were included (125 operative; 145 nonoperative). Operative treatment averaged $731/patient. Nonoperative care averaged $212/patient. Comparing operative versus nonoperative treatment, the incremental cost/DALY averted for each patient outcome was: quadriplegic ($112-$158/DALY averted), paraplegic ($47-$67/DALY averted), neurologic improvement ($50-$71/DALY averted), neurologically intact ($41-$58/DALY averted). Sensitivity analysis confirmed these findings without major differences., Conclusions: This preliminary cost-effectiveness analysis suggests that the upfront costs of spine trauma surgery may be offset by a reduction in disability. LMIC governments should consider conducting more spine trauma cost-effectiveness analyses and including spine trauma surgery in universal health care.

As of April 22, 2021, around 1.5 million individuals in three districts of Kerala, India had been vaccinated with COVID-19 vaccines. Over 80% of these individuals (1.2 million) received the ChAdOx1-S/nCoV-19 vaccine. In this population, during this period of 4 weeks (mid-March to mid-April 2021), we observed seven cases of Guillain-Barre syndrome (GBS) that occurred within 2 weeks of the first dose of vaccination. All seven patients developed severe GBS. The frequency of GBS was 1.4- to 10-fold higher than that expected in this period for a population of this magnitude. In addition, the frequency of bilateral facial weakness, which typically occurs in <20% of GBS cases, suggests a pattern associated with the vaccination. While the benefits of vaccination substantially outweigh the risk of this relatively rare outcome (5.8 per million), clinicians should be alert to this possible adverse event, as six out of seven patients progressed to areflexic quadriplegia and required mechanical ventilatory support. ANN NEUROL 2021;90:312-314., (© 2021 American Neurological Association.)

Objective: Given the high burden of neurotrauma in low- and middle-income countries (LMICs), in this observational study, the authors evaluated the treatment and outcomes of patients with severe traumatic brain injury (TBI) accessing care at the national neurosurgical institute in Tanzania., Methods: A neurotrauma registry was established at Muhimbili Orthopaedic Institute, Dar-es-Salaam, and patients with severe TBI admitted within 24 hours of injury were included. Detailed emergency department and subsequent medical and surgical management of patients was recorded. Two-week mortality was measured and compared with estimates of predicted mortality computed with admission clinical variables using the Corticoid Randomisation After Significant Head Injury (CRASH) core model., Results: In total, 462 patients (mean age 33.9 years) with severe TBI were enrolled over 4.5 years; 89% of patients were male. The mean time to arrival to the hospital after injury was 8 hours; 48.7% of patients had advanced airway management in the emergency department, 55% underwent cranial CT scanning, and 19.9% underwent surgical intervention. Tiered medical therapies for intracranial hypertension were used in less than 50% of patients. The observed 2-week mortality was 67%, which was 24% higher than expected based on the CRASH core model., Conclusions: The 2-week mortality from severe TBI at a tertiary referral center in Tanzania was 67%, which was significantly higher than the predicted estimates. The higher mortality was related to gaps in the continuum of care of patients with severe TBI, including cardiorespiratory monitoring, resuscitation, neuroimaging, and surgical rates, along with lower rates of utilization of available medical therapies. In ongoing work, the authors are attempting to identify reasons associated with the gaps in care to implement programmatic improvements. Capacity building by twinning provides an avenue for acquiring data to accurately estimate local needs and direct programmatic education and interventions to reduce excess in-hospital mortality from TBI.

The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without early treatment can succumb to delayed in-hospital care and death. Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes 1) adjuvant nutraceuticals, 2) combination intracellular anti-infective therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet agents/anticoagulants, 5) supportive care including supplemental oxygen, monitoring, and telemedicine. Randomized trials of individual, novel oral therapies have not delivered tools for physicians to combat the pandemic in practice. No single therapeutic option thus far has been entirely effective and therefore a combination is required at this time. An urgent immediate pivot from single drug to SMDT regimens should be employed as a critical strategy to deal with the large numbers of acute COVID-19 patients with the aim of reducing the intensity and duration of symptoms and avoiding hospitalization and death., Competing Interests: There is nothing to disclose. Author had access to the data and wrote the manuscript., (© 2020 McCullough et al. Published by IMR Press.)

Study Design: Retrospective, case-control study., Objectives: In a traumatic spinal injury (TSI) cohort from Tanzania, we sought to: (1) describe potential risk factors for pressure ulcer development, (2) present an illustrative case, and (3) propose a low-cost outpatient protocol for prevention and treatment., Setting: Tertiary referral hospital., Methods: All patients admitted for TSI over a 33-month period were reviewed. Variables included demographics, time to hospital, injury characteristics, operative management, length of hospitalization, and mortality. Pressure ulcer development was the primary outcome. Regressions were used to report potential predictors, and international guidelines were referenced to construct a low-cost outpatient protocol., Results: Of 267 patients that met the inclusion criteria, 51 developed a pressure ulcer. Length of stay was greater for patients with pressure ulcers compared with those without (45 vs. 30 days, p < 0.001). Potential predictors for developing pressure ulcers were: increased days from injury to hospital admission (p = 0.036), American Spinal Injury Association Impairment Scale grade A upon admission (p < 0.001), and thoracic spine injury (p = 0.037). The illustrative case described a young male presenting ~2 months after complete thoracic spinal cord injury with a grade IV sacral pressure ulcer that lead to septic shock and death. Considering the dramatic consequences of pressure ulcers in lower- and middle-income countries (LMICs), we proposed a low-cost protocol for prevention and treatment targeting support surfaces, repositioning, skin care, nutrition, follow-up, and dressing., Conclusions: Pressure ulcers after TSI in LMICs can lead to increased hospital stays and major adverse events. High-risk patients were those with delayed presentation, complete neurologic injuries, and thoracic injuries. We recommended aggressive prevention and treatment strategies suitable for resource-constrained settings.

Background: Hypertonic saline (HTS) and mannitol are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their simultaneous effect on the cerebral perfusion pressure (CPP) and ICP has not been studied rigorously., Objective: To determine the difference in effects of HTS and mannitol on the combined burden of high ICP and low CPP in patients with severe TBI., Methods: We performed a case-control study using prospectively collected data from the New York State TBI-trac® database (Brain Trauma Foundation, New York, New York). Patients who received only 1 hyperosmotic agent, either mannitol or HTS for raised ICP, were included. Patients in the 2 groups were matched (1:1 and 1:2) for factors associated with 2-wk mortality: age, Glasgow Coma Scale score, pupillary reactivity, hypotension, abnormal computed tomography scans, and craniotomy. Primary endpoint was the combined burden of ICPhigh (> 25 mm Hg) and CPPlow (< 60 mm Hg)., Results: There were 25 matched pairs for 1:1 comparison and 24 HTS patients matched to 48 mannitol patients in 1:2 comparisons. Cumulative median osmolar doses in the 2 groups were similar. In patients treated with HTS compared to mannitol, total number of days (0.6 ± 0.8 vs 2.4 ± 2.3 d, P < .01), percentage of days with (8.8 ± 10.6 vs 28.1 ± 26.9%, P < .01), and the total duration of ICPhigh + CPPlow (11.12 ± 14.11 vs 30.56 ± 31.89 h, P = .01) were significantly lower. These results were replicated in the 1:2 match comparisons., Conclusion: HTS bolus therapy appears to be superior to mannitol in reduction of the combined burden of intracranial hypertension and associated hypoperfusion in severe TBI patients., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Lyme disease is the most common tick-borne disease in Canada and the United States, caused by Borrelia burgdorferi , which affects multiple organ systems. Epidemiology, clinical presentation, and neuroimaging findings are reviewed., (© 2019 by American Journal of Neuroradiology.)

Background: Tetanus is a vaccine-preventable, neglected disease that is life threatening if acquired and occurs most frequently in regions where vaccination coverage is incomplete. Challenges in vaccination coverage contribute to the occurrence of non-neonatal tetanus in sub-Saharan countries, with high case fatality rates. The current WHO recommendations for the management of tetanus include close patient monitoring, administration of immune globulin, sedation, analgesia, wound hygiene and airway support [1]. In response to these recommendations, our tertiary referral hospital in Tanzania implemented a standardized clinical protocol for care of patients with tetanus in 2006 and a subsequent modification in 2012. In this study we aimed to assess the impact of the protocol on clinical care of tetanus patients and their outcomes., Methods and Findings: We examined provision of care and outcomes among all patients admitted with non-neonatal tetanus to the ICU at Bugando Medical Centre between 2001 and 2016 in this retrospective cohort study. We compared three groups: the pre-protocol group (2001-2005), the Early protocol group (2006-2011), and the Late protocol group (2012-2016) and determined associations with mortality by univariable logistic regression. We observed a significant increase in provision of care as per protocol between the Early and Late groups. Patients in the Late group had a significantly higher utilization of mechanical ventilation (69.9% vs 22.0%, p< 0.0001), provision of surgical wound care (39.8% vs 20.3%, p = 0.011), and performance of tracheostomies (36.8% vs 6.7%, <0.0001) than patients in the Early group. Despite the increased provision of care, we found no significant decrease in overall mortality in the Early versus the Late groups (55.4% versus 40.3%, p = 0.069), or between the pre-protocol and post-protocol groups (60.7% versus 50.0%, p = 0.28). There was also no difference in 7-day ICU mortality (30.1% versus 27.8%, p = 0.70). Analysis of the causes of death revealed a decrease in deaths related to airway compromise (30.0% to 1.8%, p<0.001) but an increase in deaths due to presumed sepsis (15.0% to 44.6%, p = 0.018)., Conclusion: The overall mortality in patients suffering non-neonatal tetanus is high (>40%). Institution of a standardized tetanus management protocol, in accordance with WHO recommendations, decreased immediate mortality related to primary causes of death after tetanus. However, this was offset by an increase in death due to later ICU complications such as sepsis. Our results illustrate the complexity in achieving mortality reduction even in illnesses thought to require few critical care interventions. Improving basic ICU care and strengthening vaccination programs to prevent tetanus altogether are essential components of efforts to decrease the mortality caused by this lethal, neglected disease., Competing Interests: The authors have declared that no competing interests exist.

Background: Data on new-onset seizures after treatment of aneurysmal subarachnoid hemorrhage (aSAH) patients are limited and variable. We examined the association between new-onset seizures after aSAH and aneurysm treatment modality, as well their relationship with initial clinical severity of aSAH and outcomes., Methods: This is a retrospective cohort study of all aSAH patients admitted to our institution over a 6-year period. 'Seizures' were defined as any observed clinical seizure or electrographic seizure on continuous electroencephalogram (cEEG) recordings, as determined by the reviewing neurophysiologist. Subgroup analyses were performed in low-grade (Hunt-Hess 1-3) and high-grade (Hunt-Hess 4-5) patients. Outcomes measures were Glasgow Coma Score (GCS) at intensive care unit (ICU) discharge and modified Rankin Scale (mRS) at outpatient follow-up., Results: There were 282 patients with aSAH; 203 (72.0%) suffered low-grade and 79 (28%) high-grade aSAH. Patients were treated with endovascular coiling (N = 194, 68.8%) or surgical clipping (N = 66, 23.4%). Eighteen (6.4%) patients had seizures, of whom 10 (5.5%) had aneurysm coiling and 7 (10.6%) underwent clipping (p = 0.15). In low-grade patients, seizures occurred less frequently (p = 0.016) and were more common after surgical clipping (p = 0.0089). Seizures correlated with lower GCS upon ICU discharge (p < 0.001), in clipped (p = 0.011) and coiled (p < 0.001) patients and in low-grade aSAH (p < 0.001). Seizures correlated with higher mRS on follow-up (p < 0.001), in clipped (p = 0.032) and coiled (p = 0.004) patients and in low-grade aSAH (p = 0.003)., Conclusions: New-onset seizures after aSAH occurred infrequently, and their incidence after aneurysm clipping versus coiling was not significantly different. However, in low-grade patients, new seizures were more frequently associated with clipping than coiling. Additionally, non-convulsive seizures did not occur in low-grade patients treated with coiling. These findings may explain, in part, previous work suggesting better outcomes in coiled patients and encourage physicians to have a lower threshold for cEEG utilization in low-grade patients suspected to have acute seizures after surgical clipping.

In the last 10 years, considerable work has been done to promote and improve neurosurgical care in East Africa with the development of national training programs, expansion of hospitals and creation of new institutions, and the foundation of epidemiologic and cost-effectiveness research. Many of the results have been accomplished through collaboration with partners from abroad. This article is the third in a series of articles that seek to provide readers with an understanding of the development of neurosurgery in East Africa (Foundations), the challenges that arise in providing neurosurgical care in developing countries (Challenges), and an overview of traditional and novel approaches to overcoming these challenges to improve healthcare in the region (Innovations). In this article, we describe the ongoing programs active in East Africa and their current priorities, and we outline lessons learned and what is required to create self-sustained neurosurgical service., (Copyright © 2018. Published by Elsevier Inc.)

This article is the first in a series of 3 articles that seek to provide readers with an understanding of the development of neurosurgery in East Africa (Foundations), the challenges that arise in providing neurosurgical care in developing countries (Challenges), and an overview of traditional and novel approaches to overcoming these challenges to improve healthcare in the region (Innovations). We review the history and evolution of neurosurgery as a clinical specialty in East Africa. We also review Kenya, Uganda, and Tanzania in some detail and highlight contributions of individuals and local and regional organizations that helped to develop and shape neurosurgical care in East Africa. Neurosurgery has developed steadily as advanced techniques have been adopted by local surgeons who trained abroad, and foreign surgeons who have dedicated part of their careers in local hospitals. New medical schools and surgical training programs have been established through regional and international partnerships, and the era of regional specialty surgical training has just begun. As more surgical specialists complete training, a comprehensive estimation of disease burden facing the neurosurgical field is important. We present an overview with specific reference to neurotrauma and neural tube defects, both of which are of epidemiologic importance as they gain not only greater recognition, but increased diagnoses and demands for treatment. Neurosurgery in East Africa is poised to blossom as it seeks to address the growing needs of a growing subspecialty., (Copyright © 2018 Elsevier Inc. All rights reserved.)

As the second of 3 articles in this series, the aim of this article is to provide readers with an understanding of the development of neurosurgery in East Africa (foundations), the challenges that arise in providing neurosurgical care in developing countries (challenges), and an overview of traditional and novel approaches to overcoming these challenges and improving health care in the region (innovations). Recognizing the challenges that need to be addressed is the first step to implementing efficient and qualified surgery delivery systems in low- and middle-income countries. We reviewed the major challenges facing health care in East Africa and grouped them into 5 categories: 1) burden of surgical disease and workforce crisis; 2) global health view of surgery as "the neglected stepchild"; 3) need for recognizing the surgical system as an interdependent network and importance of organizational and equipment deficits; 4) lack of education in the community, failure of primary care systems, and net result of overwhelming tertiary care systems; 5) personal and professional burnout as well as brain drain of promising human resources from low- and middle-income countries in East Africa and similar regions across the world. Each major challenge was detailed and analyzed by authors who have worked or are currently working in the region, providing a personal perspective., (Copyright © 2018. Published by Elsevier Inc.)

Background and Purpose: Although preclinical studies have shown inflammation to mediate perihematomal edema (PHE) after intracerebral hemorrhage, clinical data are lacking. Leukocyte count, often used to gauge serum inflammation, has been correlated with poor outcome but its relationship with PHE remains unknown. Our aim was to test the hypothesis that leukocyte count is associated with PHE growth., Methods: We included patients with intracerebral hemorrhage admitted to a tertiary-care stroke center between 2011 and 2015. The primary outcome was absolute PHE growth during 24 hours, calculated using semiautomated planimetry. Linear regression models were constructed to study the relationship between absolute and differential leukocyte counts (monocyte count and neutrophil-lymphocyte ratio) and 24-hour PHE growth., Results: A total of 153 patients were included. Median hematoma and PHE volumes at baseline were 14.4 (interquartile range, 6.3-36.3) and 14.0 (interquartile range, 5.9-27.8), respectively. In linear regression analysis adjusted for demographics and intracerebral hemorrhage characteristics, absolute leukocyte count was not associated with PHE growth (β, 0.07; standard error, 0.15; P =0.09). In secondary analyses, neutrophil-lymphocyte ratio was correlated with PHE growth (β, 0.22; standard error, 0.08; P =0.005)., Conclusions: Higher neutrophil-lymphocyte ratio is independently associated with PHE growth. This suggests that PHE growth can be predicted using differential leukocyte counts on admission., (© 2017 American Heart Association, Inc.)

Severe traumatic brain injury (TBI) causes substantial morbidity and mortality, and is a leading cause of death in both the developed and developing world. The need for a systematic evidence-based approach to the care of severe TBI patients within the emergency setting has led to its inclusion as an Emergency Neurological Life Support topic. This protocol was designed to enumerate the practice steps that should be considered within the first critical hours of neurological injury from severe TBI.

Background: Severe traumatic brain injury (TBI) is a major cause of death and disability worldwide. Prospective TBI data from sub-Saharan Africa are sparse. This study examines epidemiology and explores management of patients with severe TBI and adherence to Brain Trauma Foundation Guidelines at a tertiary care referral hospital in Tanzania., Methods: Patients with severe TBI hospitalized at Bugando Medical Centre were recorded in a prospective registry including epidemiologic, clinical, treatment, and outcome data., Results: Between September 2013 and October 2015, 371 patients with TBI were admitted; 33% (115/371) had severe TBI. Mean age was 32.0 years ± 20.1, and most patients were male (80.0%). Vehicular injuries were the most common cause of injury (65.2%). Approximately half of the patients (47.8%) were hospitalized on the day of injury. Computed tomography of the brain was performed in 49.6% of patients, and 58.3% were admitted to the intensive care unit. Continuous arterial blood pressure monitoring and intracranial pressure monitoring were not performed in any patient. Of patients with severe TBI, 38.3% received hyperosmolar therapy, and 35.7% underwent craniotomy. The 2-week mortality was 34.8%., Conclusions: Mortality of patients with severe TBI at Bugando Medical Centre, Tanzania, is approximately twice that in high-income countries. Intensive care unit care, computed tomography imaging, and continuous arterial blood pressure and intracranial pressure monitoring are underused or unavailable in the tertiary referral hospital setting. Improving outcomes after severe TBI will require concerted investment in prehospital care and improvement in availability of intensive care unit resources, computed tomography, and expertise in multidisciplinary care., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Cerebrospinal fluid diversion procedures have saved more lives than any other neurosurgical procedure. However, they do have a unique set of complications which a paediatrician in a district general hospital may encounter. Timely recognition and appropriate referral to the neurosurgeon is vital in order to avoid serious consequences and to have a favourable outcome., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: To compare outcomes after intracerebral hemorrhage (ICH) from cerebral arteriovenous malformation (AVM) rupture and other causes of ICH., Methods: We performed a retrospective population-based study using data from the Nationwide Inpatient Sample. We used standard diagnosis codes to identify ICH cases from 2002 to 2011. Our predictor variable was cerebral AVM. Our primary outcomes were inpatient mortality and home discharge. We used logistic regression to compare outcomes between patients with ICH with and without AVM while adjusting for demographics, comorbidities, and hospital characteristics. In a confirmatory analysis using a prospective cohort of patients hospitalized with ICH at our institution, we additionally adjusted for hematoma characteristics and the Glasgow Coma Scale score., Results: Among 619,167 ICH hospitalizations, the 4,485 patients (0.7%, 95% confidence interval [CI] 0.6-0.8) with an AVM were younger and had fewer medical comorbidities than patients without AVM. After adjustment for confounders, patients with AVM had lower odds of death (odds ratio [OR] 0.5, 95% CI 0.4-0.7) and higher odds of home discharge (OR 2.0, 95% CI 1.4-3.0) than patients without AVM. In a confirmatory analysis of 342 patients with ICH at our institution, the 34 patients (9.9%, 95% CI 7.2-13.6) with a ruptured AVM had higher odds of ambulatory independence at discharge (OR 4.4, 95% CI 1.4-13.1) compared to patients without AVM., Conclusions: Patients with ICH due to ruptured AVM have more favorable outcomes than patients with ICH from other causes., (© 2017 American Academy of Neurology.)

Background: Infections after intracerebral hemorrhage (ICH) may be associated with worse outcomes. We aimed to evaluate the association between nosocomial infections (>48 h) and outcomes of ICH at a population level., Methods: We identified patients with ICH using ICD-9-CM codes in the 2002-2011 Nationwide Inpatient Sample. Demographics, comorbidities, surgical procedures, and hospital characteristics were compared between patients with and without concomitant nosocomial infections. Primary outcomes were in-hospital mortality and home discharge. Secondary outcome was permanent cerebrospinal shunt placement. Logistic regression analyses were used to analyze the association between infections and outcomes., Results: Among 509,516 ICH patients, infections occurred in 117,636 (23.1 %). Rates of infections gradually increased from 18.7 % in 2002-2003 to 24.1 % in 2010-2011. Pneumonia was the most common nosocomial infection (15.4 %) followed by urinary tract infection (UTI) (7.9 %). Patients with infections were older (p < 0.001), predominantly female (56.9 % vs. 47.9 %, p < 0.001), and more often black (15.0 % vs. 13.4 %, p < 0.001). Nosocomial infection was associated with longer hospital stay (11 vs. 5 days, p < 0.001) and a more than twofold higher cost of care (p < 0.001). In the adjusted regression analysis, patients with infection had higher odds of mortality [odds ratio (OR) 2.11, 95 % CI 2.08-2.14] and cerebrospinal shunt placement (OR 2.19, 95 % CI 2.06-2.33) and lower odds of home discharge (OR 0.49, 95 % CI 0.47-0.51). Similar results were observed in subgroup analyses of individual infections., Conclusions: In a nationally representative cohort of ICH patients, nosocomial infection was associated with worse outcomes and greater resource utilization.

Background: Physicians caring for children with serious acute neurologic disease must process overwhelming amounts of physiological and medical information. Strategies to optimize real time display of this information are understudied., Objectives: Our goal was to engage clinical and engineering experts to develop guiding principles for creating a pediatric neurology intensive care unit (neuroPICU) monitor that integrates and displays data from multiple sources in an intuitive and informative manner., Methods: To accomplish this goal, an international group of physicians and engineers communicated regularly for one year. We integrated findings from clinical observations, interviews, a survey, signal processing, and visualization exercises to develop a concept for a neuroPICU display., Results: Key conclusions from our efforts include: (1) A neuroPICU display should support (a) rapid review of retrospective time series (i.e. cardiac, pulmonary, and neurologic physiology data), (b) rapidly modifiable formats for viewing that data according to the specialty of the reviewer, and (c) communication of the degree of risk of clinical decline. (2) Specialized visualizations of physiologic parameters can highlight abnormalities in multivariable temporal data. Examples include 3-D stacked spider plots and color coded time series plots. (3) Visual summaries of EEG with spectral tools (i.e. hemispheric asymmetry and median power) can highlight seizures via patient-specific "fingerprints." (4) Intuitive displays should emphasize subsets of physiology and processed EEG data to provide a rapid gestalt of the current status and medical stability of a patient., Conclusions: A well-designed neuroPICU display must present multiple datasets in dynamic, flexible, and informative views to accommodate clinicians from multiple disciplines in a variety of clinical scenarios.

Opinion Statement: Pipeline embolization device (PED) is a flow diverter used in the endovascular treatment of intracranial aneurysms, particularly those with unfavorable configurations. It works by causing progressive flow redirection leading to thrombosis within the aneurysm. PED was initially approved for adults with large or giant wide-necked (≥4 mm or no discernible neck) aneurysms of the internal carotid artery (ICA) from the petrous to the superior hypophyseal segments. Studies have shown a superior aneurysm occlusion rate of 85 % at 6 months for the PED and mortality ranging from 2.6 to 4 %. There appears to be a knowledge gap in terms of the duration of dual antiplatelet therapy and efficacy of assessing platelet inhibition. However, increasing operator experience and favorable longer-term outcome data have led to the exploration of PED for a wide array of off-label uses. Given the paucity of good-quality studies comparing PED with other endovascular/surgical treatment options, several multicenter randomized trials are currently underway to answer these important questions.

Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.

Background: Mechanical ventilation is frequently performed in patients with ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). In this study, we used statewide administrative claims data to examine the rates of use, associated conditions, and in-hospital mortality rates for mechanically ventilated stroke patients., Methods: We used statewide administrative claims data from three states and ICD-9-CM codes to identify patients admitted with stroke and those who received mechanical ventilation and tracheostomy. Descriptive statistics and exact 95 % confidence intervals were used to report rates of mechanical ventilation, tracheostomy, and in-hospital mortality. Logistic regression analysis was performed to identify conditions associated with mechanical ventilation based on previously described risk factors., Results: 798,255 hospital admissions for stroke were identified. 12.5 % of these patients underwent mechanical ventilation. This rate varied by stroke type: 7.9 % for IS, 29.9 % for ICH, and 38.5 % for SAH. Increased age was associated with a decreased risk of receiving mechanical ventilation (RR per decade, 0.91). Of stroke patients who underwent mechanical ventilation, 16.3 % received a tracheostomy. Mechanical ventilation was more likely to occur in association with status epilepticus (RR, 5.1), pneumonia (RR, 4.9), sepsis (RR, 3.6), and hydrocephalus (RR, 3.3). In-hospital mortality rate for mechanically ventilated stroke patients was 52.7 % (46.8 % for IS, 61.0 % for ICH, and 54.6 % for SAH)., Conclusions: In this large population-based sample, over half of mechanically ventilated stroke patients died in the hospital despite the fact that younger patients were more likely to receive mechanical ventilation. Future studies are indicated to elucidate mechanical ventilation strategies to optimize long-term outcomes after severe stroke.

Hyperosmolar agents are commonly used as an initial treatment for the management of raised intracranial pressure (ICP) after severe traumatic brain injury (TBI). They have an excellent adverse-effect profile compared to other therapies, such as hyperventilation and barbiturates, which carry the risk of reducing cerebral perfusion. The hyperosmolar agent mannitol has been used for several decades to reduce raised ICP, and there is accumulating evidence from pilot studies suggesting beneficial effects of hypertonic saline (HTS) for similar purposes. An ideal therapeutic agent for ICP reduction should reduce ICP while maintaining cerebral perfusion (pressure). While mannitol can cause dehydration over time, HTS helps maintain normovolemia and cerebral perfusion, a finding that has led to a large amount of pilot data being published on the benefits of HTS, albeit in small cohorts. Prophylactic therapy is not recommended with mannitol, although it may be beneficial with HTS. To date, no large clinical trial has been performed to directly compare the two agents. The best current evidence suggests that mannitol is effective in reducing ICP in the management of traumatic intracranial hypertension and carries mortality benefit compared to barbiturates. Current evidence regarding the use of HTS in severe TBI is limited to smaller studies, which illustrate a benefit in ICP reduction and perhaps mortality., (© 2015 New York Academy of Sciences.)

Object: Increased intracranial pressure (ICP) in patients with traumatic brain injury (TBI) is associated with a higher mortality rate and poor outcome. Mannitol and hypertonic saline (HTS) have both been used to treat high ICP, but it is unclear which one is more effective. Here, the authors compare the effect of mannitol versus HTS on lowering the cumulative and daily ICP burdens after severe TBI., Methods: The Brain Trauma Foundation TBI-trac New York State database was used for this retrospective study. Patients with severe TBI and intracranial hypertension who received only 1 type of hyperosmotic agent, mannitol or HTS, were included. Patients in the 2 groups were individually matched for Glasgow Coma Scale score (GCS), pupillary reactivity, craniotomy, occurrence of hypotension on Day 1, and the day of ICP monitor insertion. Patients with missing or erroneous data were excluded. Cumulative and daily ICP burdens were used as primary outcome measures. The cumulative ICP burden was defined as the total number of days with an ICP of > 25 mm Hg, expressed as a percentage of the total number of days of ICP monitoring. The daily ICP burden was calculated as the mean daily duration of an ICP of > 25 mm Hg, expressed as the number of hours per day. The numbers of intensive care unit (ICU) days, numbers of days with ICP monitoring, and 2-week mortality rates were also compared between the groups. A 2-sample t-test or chi-square test was used to compare independent samples. The Wilcoxon signed-rank or Cochran-Mantel-Haenszel test was used for comparing matched samples., Results: A total of 35 patients who received only HTS and 477 who received only mannitol after severe TBI were identified. Eight patients in the HTS group were excluded because of erroneous or missing data, and 2 other patients did not have matches in the mannitol group. The remaining 25 patients were matched 1:1. Twenty-four patients received 3% HTS, and 1 received 23.4% HTS as bolus therapy. All 25 patients in the mannitol group received 20% mannitol. The mean cumulative ICP burden (15.52% [HTS] vs 36.5% [mannitol]; p = 0.003) and the mean (± SD) daily ICP burden (0.3 ± 0.6 hours/day [HTS] vs 1.3 ± 1.3 hours/day [mannitol]; p = 0.001) were significantly lower in the HTS group. The mean (± SD) number of ICU days was significantly lower in the HTS group than in the mannitol group (8.5 ± 2.1 vs 9.8 ± 0.6, respectively; p = 0.004), whereas there was no difference in the numbers of days of ICP monitoring (p = 0.09). There were no significant differences between the cumulative median doses of HTS and mannitol (p = 0.19). The 2-week mortality rate was lower in the HTS group, but the difference was not statistically significant (p = 0.56)., Conclusions: HTS given as bolus therapy was more effective than mannitol in lowering the cumulative and daily ICP burdens after severe TBI. Patients in the HTS group had significantly lower number of ICU days. The 2-week mortality rates were not statistically different between the 2 groups.

Background and Purpose: In recent years CTP has been used as a complementary diagnostic tool in the evaluation of delayed cerebral ischemia and vasospasm. Our aim was to determine the test characteristics of CTP for detecting delayed cerebral ischemia and vasospasm in SAH, and then to apply Bayesian analysis to identify subgroups for its appropriate use., Materials and Methods: Our retrospective cohort comprised consecutive patients with SAH and CTP performed between days 6 and 8 following aneurysm rupture. Delayed cerebral ischemia was determined according to primary outcome measures of infarction and/or permanent neurologic deficits. Vasospasm was determined by using DSA. The test characteristics of CTP and its 95% CIs were calculated. Graphs of conditional probabilities were constructed by using Bayesian techniques. Local treatment thresholds (posttest probability of delayed cerebral ischemia needed to initiate induced hypertension, hypervolemia, and hemodilution or intra-arterial therapy) were determined via a survey of 6 independent neurologists., Results: Ninety-seven patients with SAH were included in the study; 39% (38/97) developed delayed cerebral ischemia. Qualitative CTP deficits were seen in 49% (48/97), occurring in 84% (32/38) with delayed cerebral ischemia and 27% (16/59) without. The sensitivity, specificity, and positive and negative predictive values (95% CI) for CTP were 0.84 (0.73-0.96), 0.73 (0.62-0.84), 0.67 (0.51-0.79), and 0.88 (0.74-0.94), respectively. A subgroup of 57 patients underwent DSA; 63% (36/57) developed vasospasm. Qualitative CTP deficits were seen in 70% (40/57), occurring in 97% (35/36) with vasospasm and 23% (5/21) without. The sensitivity, specificity, and positive and negative predictive values (95% CI) for CTP were 0.97 (0.92-1.0), 0.76 (0.58-0.94), 0.88 (0.72-0.95), and 0.94 (0.69-0.99), respectively. Treatment thresholds were determined as 30% for induced hypertension, hypervolemia, and hemodilution and 70% for intra-arterial therapy., Conclusions: Positive CTP findings identify patients who should be carefully considered for induced hypertension, hypervolemia, and hemodilution and/or intra-arterial therapy while negative CTP findings are useful in guiding a no-treatment decision.

Objectives: Shivering after anesthesia or in the critical care setting is frequent, can be prolonged, and has the potential for serious adverse events and worsening outcomes. Furthermore, there are conflicting published data and clinical protocols on how to best treat shivering. In this study, we aimed to critically analyze the published evidence of antishivering medications., Data Sources: We systematically reviewed, categorized, and analyzed all literature on antishivering medications published in English. Target key words and study types were determined and major scientific databases (PubMed, EMBASE, the Cochrane Controlled Trials Register, Ovid-Medline, and JAMA Evidence) and individual target journals were systematically searched up to August 1, 2011., Study Selection: Publications were categorized by the pharmacological intervention used, regardless of whether the subjects were ventilated, underwent surgery, received anesthesia, or received additional medications. Randomized, double-blinded, placebo-controlled trials investigating antishivering treatment were extracted and evaluated for clinical and statistical homogeneity and, if suitable, included in a subsequent meta-analysis using linear comparisons calculating shivering risk-reduction ratios., Data Extraction: A total of 41 individual and eight combination antishivering medications were tested in 124 publications containing 208 substudies and recruiting a total of 9,668 subjects. Among those, 80 publications containing 119 substudies were identified as randomized, double-blinded, placebo-controlled of which 94 substudies were subjected to linear comparison analysis., Data Synthesis: Study drug frequencies, calculated pooled risk benefits, and pooled numbers needed to treat of the five most frequently studied and efficacious medications were clonidine (22 studies; risk ratio: 1.6, numbers needed to treat: 4), meperidine (16; 2.2, 2), tramadol (8; 2.2, 2), nefopam (7; 2.1, 2), and ketamine (7; 1.8, 3)., Conclusions: There is significant heterogeneity in the literature with respect to study methods and efficacy testing of antishivering treatments. Clonidine, meperidine, tramadol, nefopam, and ketamine were the most frequently reported pharmacological interventions and showed a variable degree of efficacy in randomized, double-blinded, placebo-controlled trials.

The majority of burn injuries in the pediatric population occur at home, and a significant proportion are the result of exposure to household cleaning products. A common injury-causing agent is bleach, which has the potential to release chlorine gas, a potent respiratory irritant that leads to the added risk of inhalation injury. The survival of pediatric patients with chemical burns is extremely high, and the 3 strongest predictors of mortality are large burn size, age <48 months, and the presence of inhalation injury. The authors present a rare case of a pediatric fatality from a chemical bleach burn that resulted in acute respiratory distress syndrome as well as hemodynamic and pulmonary instability that required extracorporeal membrane oxygenation. The authors critically appraised the management of this patient to determine the possible effect certain events had on the unexpected and poor outcome of this patient, including fluid resuscitation, the effect of the chemical inhalation injury, sedation, and the need for invasive extracorporeal membrane oxygenation life support.