Prehospital Management of Traumatic Brain Injury across Europe: A CENTER-TBI Study.

BACKGROUND: Prehospital care for traumatic brain injury (TBI) is important to prevent secondary brain injury. We aim to compare prehospital care systems within Europe and investigate the association of system characteristics with the stability of patients at hospital arrival. METHODS: We studied TBI patients who were transported to CENTER-TBI centers, a pan-European, prospective TBI cohort study, by emergency medical services between 2014 and 2017. The association of demographic factors, injury severity, situational factors, and interventions associated with on-scene time was assessed using linear regression. We used mixed effects models to investigate the case mix adjusted variation between countries in prehospital times and interventions. The case mix adjusted impact of on-scene time and interventions on hypoxia (oxygen saturation <90%) and hypotension (systolic blood pressure <100mmHg) at hospital arrival was analyzed with logistic regression. RESULTS: Among 3878 patients, the greatest driver of longer on-scene time was intubation (+8.3 min, 95% CI: 5.6-11.1). Secondary referral was associated with shorter on-scene time (-5.0 min 95% CI: -6.2- -3.8). Between countries, there was a large variation in response (range: 12-25 min), on-scene (range: 16-36 min) and travel time (range: 15-32 min) and in prehospital interventions. These variations were not explained by patient factors such as conscious level or severity of injury (expected OR between countries: 1.8 for intubation, 1.8 for IV fluids, 2.0 for helicopter). On-scene time was not associated with the regional EMS policy (p= 0.58). Hypotension and/or hypoxia were seen in 180 (6%) and 97 (3%) patients in the overall cohort and in 13% and 7% of patients with severe TBI (GCS <8). The largest association with secondary insults at hospital arrival was with major extracranial injury: the OR was 3.6 (95% CI: 2.6-5.0) for hypotension and 4.4 (95% CI: 2.9-6.7) for hypoxia. DISCUSSION: Hypoxia and hypotension continue to occur in patients who suffer a TBI, and remain relatively common in severe TBI. Substantial variation in prehospital care exists for patients after TBI in Europe, which is only partially explained by patient factors.

Neurological outcome after extracorporeal cardiopulmonary resuscitation for in-hospital cardiac arrest: a systematic review and meta-analysis.

BACKGROUND: In-hospital cardiac arrest (IHCA) is a major adverse event with a high mortality rate if not treated appropriately. Extracorporeal cardiopulmonary resuscitation (ECPR), as adjunct to conventional cardiopulmonary resuscitation (CCPR), is a promising technique for IHCA treatment. Evidence pertaining to neurological outcomes after ECPR is still scarce. METHODS: We performed a comprehensive systematic search of all studies up to December 20, 2019. Our primary outcome was neurological outcome after ECPR at any moment after hospital discharge, defined by the Cerebral Performance Category (CPC) score. A score of 1 or 2 was defined as favourable outcome. Our secondary outcome was post-discharge mortality. A fixed-effects meta-analysis was performed. RESULTS: Our search yielded 1215 results, of which 19 studies were included in this systematic review. The average survival rate was 30% (95% CI 28-33%, I2 = 0%, p = 0.24). In the surviving patients, the pooled percentage of favourable neurological outcome was 84% (95% CI 80-88%, I2 = 24%, p = 0.90). CONCLUSION: ECPR as treatment for in-hospital cardiac arrest is associated with a large proportion of patients with good neurological outcome. The large proportion of favourable outcome could potentially be explained by the selection of patients for treatment using ECPR. Moreover, survival is higher than described in the conventional CPR literature. As indications for ECPR might extend to older or more fragile patient populations in the future, research should focus on increasing survival, while maintaining optimal neurological outcome.

Tracheal intubation in traumatic brain injury: a multicentre prospective observational study.

BACKGROUND: We aimed to study the associations between pre- and in-hospital tracheal intubation and outcomes in traumatic brain injury (TBI), and whether the association varied according to injury severity. METHODS: Data from the international prospective pan-European cohort study, Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI), were used (n=4509). For prehospital intubation, we excluded self-presenters. For in-hospital intubation, patients whose tracheas were intubated on-scene were excluded. The association between intubation and outcome was analysed with ordinal regression with adjustment for the International Mission for Prognosis and Analysis of Clinical Trials in TBI variables and extracranial injury. We assessed whether the effect of intubation varied by injury severity by testing the added value of an interaction term with likelihood ratio tests. RESULTS: In the prehospital analysis, 890/3736 (24%) patients had their tracheas intubated at scene. In the in-hospital analysis, 460/2930 (16%) patients had their tracheas intubated in the emergency department. There was no adjusted overall effect on functional outcome of prehospital intubation (odds ratio=1.01; 95% confidence interval, 0.79-1.28; P=0.96), and the adjusted overall effect of in-hospital intubation was not significant (odds ratio=0.86; 95% confidence interval, 0.65-1.13; P=0.28). However, prehospital intubation was associated with better functional outcome in patients with higher thorax and abdominal Abbreviated Injury Scale scores (P=0.009 and P=0.02, respectively), whereas in-hospital intubation was associated with better outcome in patients with lower Glasgow Coma Scale scores (P=0.01): in-hospital intubation was associated with better functional outcome in patients with Glasgow Coma Scale scores of 10 or lower. CONCLUSION: The benefits and harms of tracheal intubation should be carefully evaluated in patients with TBI to optimise benefit. This study suggests that extracranial injury should influence the decision in the prehospital setting, and level of consciousness in the in-hospital setting. CLINICAL TRIAL REGISTRATION: NCT02210221.

Development and internal validation of a clinical prediction model using machine learning algorithms for 90 day and 2 year mortality in femoral neck fracture patients aged 65 years or above.

PURPOSE: Preoperative prediction of mortality in femoral neck fracture patients aged 65 years or above may be valuable in the treatment decision-making. A preoperative clinical prediction model can aid surgeons and patients in the shared decision-making process, and optimize care for elderly femoral neck fracture patients. This study aimed to develop and internally validate a clinical prediction model using machine learning (ML) algorithms for 90 day and 2 year mortality in femoral neck fracture patients aged 65 years or above. METHODS: A retrospective cohort study at two trauma level I centers and three (non-level I) community hospitals was conducted to identify patients undergoing surgical fixation for a femoral neck fracture. Five different ML algorithms were developed and internally validated and assessed by discrimination, calibration, Brier score and decision curve analysis. RESULTS: In total, 2478 patients were included with 90 day and 2 year mortality rates of 9.1% (n = 225) and 23.5% (n = 582) respectively. The models included patient characteristics, comorbidities and laboratory values. The stochastic gradient boosting algorithm had the best performance for 90 day mortality prediction, with good discrimination (c-statistic = 0.74), calibration (intercept = - 0.05, slope = 1.11) and Brier score (0.078). The elastic-net penalized logistic regression algorithm had the best performance for 2 year mortality prediction, with good discrimination (c-statistic = 0.70), calibration (intercept = - 0.03, slope = 0.89) and Brier score (0.16). The models were incorporated into a freely available web-based application, including individual patient explanations for interpretation of the model to understand the reasoning how the model made a certain prediction: https://sorg-apps.shinyapps.io/hipfracturemortality/ CONCLUSIONS: The clinical prediction models show promise in estimating mortality prediction in elderly femoral neck fracture patients. External and prospective validation of the models may improve surgeon ability when faced with the treatment decision-making. LEVEL OF EVIDENCE: Prognostic Level II.

Missing Data in Prediction Research: A Five-Step Approach for Multiple Imputation, Illustrated in the CENTER-TBI Study.

In medical research, missing data is common. In acute diseases, such as traumatic brain injury (TBI), even well-conducted prospective studies may suffer from missing data in baseline characteristics and outcomes. Statistical models may simply drop patients with any missing values, potentially leaving a selected subset of the original cohort. Imputation is widely accepted by methodologists as an appropriate way to deal with missing data. We aim to provide practical guidance on handling missing data for prediction modeling. We hereto propose a five-step approach, centered around single and multiple imputation: 1) explore the missing data patterns; 2) choose a method of imputation; 3) perform imputation; 4) assess diagnostics of the imputation; and 5) analyze the imputed data sets. We illustrate these five steps with the estimation and validation of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury) prognostic model in 1375 patients from the CENTER-TBI database, included in 53 centers across 17 countries, with moderate or severe TBI in the prospective European CENTER-TBI study. Future prediction modeling studies in acute diseases may benefit from following the suggested five steps for optimal statistical analysis and interpretation, after maximal effort has been made to minimize missing data.

Primary versus early secondary referral to a specialized neurotrauma center in patients with moderate/severe traumatic brain injury: a CENTER TBI study.

BACKGROUND: Prehospital care for patients with traumatic brain injury (TBI) varies with some emergency medical systems recommending direct transport of patients with moderate to severe TBI to hospitals with specialist neurotrauma care (SNCs). The aim of this study is to assess variation in levels of early secondary referral within European SNCs and to compare the outcomes of directly admitted and secondarily transferred patients. METHODS: Patients with moderate and severe TBI (Glasgow Coma Scale < 13) from the prospective European CENTER-TBI study were included in this study. All participating hospitals were specialist neuroscience centers. First, adjusted between-country differences were analysed using random effects logistic regression where early secondary referral was the dependent variable, and a random intercept for country was included. Second, the adjusted effect of early secondary referral on survival to hospital discharge and functional outcome [6 months Glasgow Outcome Scale Extended (GOSE)] was estimated using logistic and ordinal mixed effects models, respectively. RESULTS: A total of 1347 moderate/severe TBI patients from 53 SNCs in 18 European countries were included. Of these 1347 patients, 195 (14.5%) were admitted after early secondary referral. Secondarily referred moderate/severe TBI patients presented more often with a CT abnormality: mass lesion (52% vs. 34%), midline shift (54% vs. 36%) and acute subdural hematoma (77% vs. 65%). After adjusting for case-mix, there was a large European variation in early secondary referral, with a median OR of 1.69 between countries. Early secondary referral was not associated with functional outcome (adjusted OR 1.07, 95% CI 0.78-1.69), nor with survival at discharge (1.05, 0.58-1.90). CONCLUSIONS: Across Europe, substantial practice variation exists in the proportion of secondarily referred TBI patients at SNCs that is not explained by case mix. Within SNCs early secondary referral does not seem to impact functional outcome and survival after stabilisation in a non-specialised hospital. Future research should identify which patients with TBI truly benefit from direct transportation.

One-year survival after in-hospital cardiac arrest: A systematic review and meta-analysis.

INTRODUCTION: In-hospital cardiac arrest is a major adverse event with an incidence of 1-6/1000 admissions. It has been poorly researched and data on survival is limited. The outcome of interest in IHCA research is predominantly survival to discharge, however recent guidelines warrant for more long-term outcomes. In this systematic review we sought to quantitatively summarize one-year survival after in-hospital cardiac arrest. METHODS: For this systematic review and meta-analysis we performed a systematic search of all published data on one-year survival after IHCA up to March 9th, 2018. Results of the meta-analyses are presented as pooled proportions with corresponding 95% prediction intervals (95%PI). Between-study heterogeneity was assessed using I2 statistic and the DerSimonian-Laird estimator for τ2. Subgroup analyses were performed for cardiac and non-cardiac patients. RESULTS: We included 40 studies in our systematic review and meta-analysis. The pooled one-year survival after in-hospital cardiac arrest was 13.4% (95%PI: 5.6-28.8%, I2 = 100%). Subgroup analysis of cardiac patients revealed a one-year survival of 39.3% (16.1%-68.6%) in patients with a non-cardiac admission characteristic one-year survival was 10.7% (4.4%-23.6%). These data cover the period 1985-2018 and show a modest change in survival over that period (10-year OR: 1.70, 95% CI: 1.04-2.76). DISCUSSION: One-year survival after in-hospital cardiac arrest is poor. Survival is higher in patients admitted to cardiac wards. The time trend between 1985-2018 has shown a modest improvement in one-year survival rates. Research into IHCA population characteristics might elicit the issue of heterogeneity and stagnated survival over the past decades.