The Pediatric Guideline Adherence and Outcomes (PEGASUS Argentina) program in severe traumatic brain injury: study protocol adaptations during the COVID-19 pandemic for a multisite implementation-effectiveness cluster randomized controlled trial.

BACKGROUND: The aim of this protocol is to describe the study protocol changes made and subsequently implemented to the Pediatric Guideline Adherence and Outcomes (PEGASUS) Argentina randomized controlled trial (RCT) for care of children with severe traumatic brain injuries (TBI) imposed by the COVID-19 pandemic. The PEGASUS study group met in spring 2020 to evaluate available literature review guidance and the study design change or pausing options due to the potential interruption of research. METHODS: As a parallel cluster RCT, pediatric patients with severe TBIs are admitted to 8 control (usual care) and 8 intervention (PEGASUS program) hospitals in Argentina, Chile, and Paraguay. PEGASUS is an intervention that aims to increase guideline adherence and best practice care for improving patient outcomes using multi-level implementation science-based approaches. Strengths and weaknesses of proposed options were assessed and resulted in a decision to revert from a stepped wedge to a parallel cluster RCT but to not delay planned implementation. DISCUSSION: The parallel cluster design was considered more robust and flexible to secular interruptions and acceptable and feasible to the local study sites in this situation. Due to the early stage of the study, the team had flexibility to redesign and implement a design more compatible with the conditions of the research landscape in 2020 while balancing analytical methods and power, logistical and implementation feasibility, and acceptability. As of fall 2022, the PEGASUS RCT has been active for nearly 2 years of implementation and data collection, scheduled to be completed in in fall 2023. The experience of navigating research during this period will influence decisions about future research design, strategies, and contingencies. TRIAL REGISTRATION: Pediatric Guideline Adherence and Outcomes-Argentina. Registered with ClinicalTrials.gov Identifier NCT03896789 on April 1, 2019.

Performance validity testing via telehealth and failure rate in veterans with moderate-to-severe traumatic brain injury: A veterans affairs TBI model systems study.

BACKGROUND: The COVID-19 pandemic has led to increased utilization of teleneuropsychology (TeleNP) services. Unfortunately, investigations of performance validity tests (PVT) delivered via TeleNP are sparse. OBJECTIVE: The purpose of this study was to examine the specificity of the Reliable Digit Span (RDS) and 21-item test administered via telephone. METHOD: Participants were 51 veterans with moderate-to-severe traumatic brain injury (TBI). All participants completed the RDS and 21-item test in the context of a larger TeleNP battery. Specificity rates were examined across multiple cutoffs for both PVTs. RESULTS: Consistent with research employing traditional face-to-face neuropsychological evaluations, both PVTs maintained adequate specificity (i.e., > 90%) across previously established cutoffs. Specifically, defining performance invalidity as RDS < 7 or 21-item test forced choice total correct < 11 led to < 10%false positive classification errors. CONCLUSIONS: Findings add to the limited body of research examining and provide preliminary support for the use of the RDS and 21-item test in TeleNP via telephone. Both measures maintained adequate specificity in veterans with moderate-to-severe TBI. Future investigations including clinical or experimental "feigners" in a counter-balanced cross-over design (i.e., face-to-face vs. TeleNP) are recommended.

Head home: implementation during COVID-19 pandemic.

BACKGROUND: Recent research suggests that between 20% and 50% of paediatric head injuries attending our emergency department (ED) could be safely discharged soon after triage, without the need for medical review, using a 'Head Injury Discharge At Triage' tool (HIDAT). We sought to implement this into clinical practice. METHODS: Paediatric ED triage staff underwent competency-based assessments for HIDAT with all head injury presentations 1 May to 31 October 2020 included in analysis. We determined which patients were discharged using the tool, which underwent CT of the brain and whether there was a clinically important traumatic brain injury or representation to the ED. RESULTS: Of the 1429 patients screened; 610 (43%) screened negative with 250 (18%) discharged by nursing staff. Of the entire cohort, 32 CTs were performed for head injury concerns (6 abnormal) with 1 CT performed in the HIDAT negative group (normal). Of those discharged using HIDAT, four reattended, two with vomiting (no imaging or admission) and two with minor scalp wound infections. Two patients who screened negative declined discharge under the policy with later medical discharge (no imaging or admission). Paediatric ED attendances were 29% lower than in 2018. CONCLUSION: We have successfully implemented HIDAT into local clinical practice. The number discharged (18%) is lower than originally described; this is likely multifactorial. The relationship between COVID-19 and paediatric ED attendances is unclear but decreased attendances suggest those for whom the tool was originally designed are not attending ED and may be accessing other medical/non-medical resources.

The Effects of Lockdown During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pandemic on Neurotrauma-Related Hospital Admissions.

BACKGROUND: The response to the global severe acute respiratory syndrome coronavirus 2 pandemic culminated in mandatory isolation throughout the world, with nationwide confinement orders issued to decrease viral spread. These drastic measures were successful in "flattening the curve" and maintaining the previous rate of coronavirus disease 2019 infections and deaths. To date, the effects of the coronavirus disease 2019 pandemic on neurotrauma has not been reported. METHODS: We retrospectively analyzed hospital admissions from Ryder Trauma Center at Jackson Memorial Hospital, during the months of March and April from 2016 to 2020. Specifically, we identified all patients who had cranial neurotrauma consisting of traumatic brain injury and/or skull fractures, as well as spinal neurotrauma consisting of vertebral fractures and/or spinal cord injury. We then performed chart review to determine mechanism of injury and if emergent surgical intervention was required. RESULTS: Compared with previous years, we saw a significant decline in the number of neurotraumas during the pandemic, with a 62% decline after the lockdown began. The number of emergent neurotrauma surgical cases also significantly decreased by 84% in the month of April. Interestingly, although the number of vehicular traumas decreased by 77%, there was a significant 100% increase in the number of gunshot wounds. CONCLUSIONS: Population seclusion had a direct effect on the frequency of neurotrauma, whereas the change in relative proportion of certain mechanisms may be associated with the psychosocial effects of social distancing and quarantine.

The Role of NLRP3 Inflammasome in the Pathogenesis of Traumatic Brain Injury.

Traumatic brain injury (TBI) represents an important problem of global health. The damage related to TBI is first due to the direct injury and then to a secondary phase in which neuroinflammation plays a key role. NLRP3 inflammasome is a component of the innate immune response and different diseases, such as neurodegenerative diseases, are characterized by NLRP3 activation. This review aims to describe NLRP3 inflammasome and the consequences related to its activation following TBI. NLRP3, caspase-1, IL-1ß, and IL-18 are significantly upregulated after TBI, therefore, the use of nonspecific, but mostly specific NLRP3 inhibitors is useful to ameliorate the damage post-TBI characterized by neuroinflammation. Moreover, NLRP3 and the molecules associated with its activation may be considered as biomarkers and predictive factors for other neurodegenerative diseases consequent to TBI. Complications such as continuous stimuli or viral infections, such as the SARS-CoV-2 infection, may worsen the prognosis of TBI, altering the immune response and increasing the neuroinflammatory processes related to NLRP3, whose activation occurs both in TBI and in SARS-CoV-2 infection. This review points out the role of NLRP3 in TBI and highlights the hypothesis that NLRP3 may be considered as a potential therapeutic target for the management of neuroinflammation in TBI.

The influence of the COVID-19 pandemic on traumatic brain injuries in Tyrol: experiences from a state under lockdown.

PURPOSE: In February 2020, the federal state of Tyrol in Austria has become one of the epicenters of the COVID-19 pandemic. Tyrol is known for numerous skiing areas. Thus, winter sport resorts became a starting point for COVID-19 infections spreading towards the rest of the state, Austria and other countries, leading to a mandatory quarantine for almost a million people, who were placed under a curfew and restrictions in daily life. Additionally, all ski resorts and hotels were closed. We aimed to analyze the influence of the COVID-19 quarantine on traumatic brain injury (TBI) cases in Tyrol. METHODS: We retrospectively compared demographical and injury characteristics from all TBI patients within the 2020 strict quarantine period with the respective time periods from 2016 to 2019. As our department is the only neurosurgical unit in Tyrol, all patients with moderate or severe TBI are transferred to our hospital. RESULTS: During 3 weeks of the full quarantine period, the weekly TBI cases load decreased significantly in comparison to the same time periods in the years 2016-2019. Furthermore, concomitant skull fractures decreased significantly (p < 0.016), probably reflecting different causative mechanisms. The other demographical and injury characteristics and particularly falls at home stayed relatively unchanged. CONCLUSION: TBI remained an important contributor to the neurosurgical workflow during the COVID-19 pandemic. Strategies to ensure neurosurgical care also under pandemic-induced lockdown are important.

A Systematic Review and Meta-Analysis of Hypothermia in Experimental Traumatic Brain Injury: Why Have Promising Animal Studies Not Been Replicated in Pragmatic Clinical Trials?

Therapeutic hypothermia was a mainstay of severe traumatic brain injury (TBI) management for half a century. Recent trials have suggested that its effect on long-term functional outcome is neutral or negative, despite apparently promising pre-clinical data. Systematic review and meta-analysis is a useful tool to collate experimental data and investigate the basis of its conclusions. We searched three online databases to identify studies testing systemic hypothermia as monotherapy for treatment of animals subjected to a TBI. Data pertaining to TBI paradigm, animal subjects, and hypothermia management were extracted as well as those relating to risk of bias. We pooled outcome data where sufficient numbers allowed and investigated heterogeneity in neurobehavioral outcomes using multi-variate meta-regression. We identified 90 publications reporting 272 experiments testing hypothermia in animals subject to TBI. The subjects were mostly small animals, with well-established models predominating. Target temperature was comparable to clinical trial data but treatment was initiated very early. Study quality was low and there was some evidence of publication bias. Delay to treatment, comorbidity, and blinded outcome assessment appeared to predict neurobehavioral outcome on multi-variate meta-regression. Therapeutic hypothermia appears to be an efficacious treatment in experimental TBI, which differs from the clinical evidence. The pre-clinical literature showed limitations in quality and design and these both appeared to affect neurobehavioral experiment outcome. These should be acknowledged when designing and interpreting pre-clinical TBI studies in the future.