A Model Predicting the 6-Month Disability of Patients With Traumatic Brain Injury to Assess the Quality of Care in Intensive Care Units: Results from the CREACTIVE Study.

Assessing quality of care is essential for improving the management of patients experiencing traumatic brain injury (TBI). This study aimed at devising a rigorous framework to evaluate the quality of TBI care provided by intensive care units (ICUs) and applying it to the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) consortium, which involved 83 ICUs from seven countries. The performance of the centers was assessed in terms of patients' outcomes, as measured by the 6-month Glasgow Outcome Scale-Extended (GOS-E). To account for the between-center differences in the characteristics of the admitted patients, we developed a multinomial logistic regression model estimating the probability of a four-level categorization of the GOS-E: good recovery (GR), moderate disability (MD), severe disability (SD), and death or vegetative state (D/VS). A total of 5928 patients admitted to the participating ICUs between March 2014 and March 2019 were analyzed. The model included 11 predictors and demonstrated good discrimination (area under the receiver operating characteristic [ROC] curve in the validation set for GR: 0.836, MD: 0.802, SD: 0.706, D/VS: 0.890) and calibration, both overall (Hosmer-Lemeshow test p value: 0.87) and in several subgroups, defined by prognostically relevant variables. The model was used as a benchmark for assessing quality of care by comparing the observed number of patients experiencing GR, MD, SD, and D/VS to the corresponding numbers expected in each category by the model, computing observed/expected (O/E) ratios. The four center-specific ratios were assembled with polar representations and used to provide a multidimensional assessment of the ICUs, overcoming the loss of information consequent to the traditional dichotomizations of the outcome in TBI research. The proposed framework can help in identifying strengths and weaknesses of current TBI care, triggering the changes that are necessary to improve patient outcomes.

Comparative Effectiveness of Intracranial Pressure Monitoring on 6-Month Outcomes of Critically Ill Patients With Traumatic Brain Injury.

Importance: While the relationship between persistent elevations in intracranial pressure (ICP) and poorer outcomes is well established for patients with traumatic brain injury (TBI), there is no consensus on how ICP measurements should drive treatment choices, and the effectiveness of ICP monitoring remains unknown. Objective: To evaluate the effectiveness of ICP monitoring on short- and mid-term outcomes of patients with TBI. Design, Setting, and Participants: CREACTIVE was a prospective cohort study that started in March 2014 and lasted 5 years. More than 8000 patients with TBI were enrolled at 83 intensive care units (ICUs) from 7 countries who joined the CREACTIVE Consortium. Patients with TBI who met the Brain Trauma Foundation guidelines for ICP monitoring were selected for the current analyses, which were performed from January to November 2022. Exposure: Patients who underwent ICP monitoring within 2 days of injury (exposure group) were propensity score-matched to patients who were not monitored or who underwent monitoring 2 days after the injury (control group). Main Outcome and Measure: Functional disability at 6 months as indicated by Glasgow Outcome Scale-Extended (GOS-E) score. Results: A total of 1448 patients from 43 ICUs in Italy and Hungary were eligible for analysis. Of the patients satisfying the ICP-monitoring guidelines, 503 (34.7%) underwent ICP monitoring (median [IQR] age: 45 years [29-61 years]; 392 males [77.9%], 111 females [22.1%]) and 945 were not monitored (median [IQR] age: 66 years [48-78 years]; 656 males [69.4%], 289 females [30.6%]). After matching to balance the variables, worse 6-month recovery was observed for monitored patients compared with nonmonitored patients (death/vegetative state: 39.2% vs 40.6%; severe disability: 33.2% vs 25.4%; moderate disability: 15.7% vs 14.9%; good recovery: 11.9% vs 19.1%, respectively; P = .005). Monitored patients received medical therapies significantly more frequently. Conclusions and Relevance: In this cohort study, ICP monitoring was associated with poorer recovery and more frequent medical interventions with their relevant adverse effects. Optimizing the value of ICP monitoring for TBI requires further investigation on monitoring indications, clinical interventions, and management protocols.

Epidemiology of neuronal surface antibody-mediated autoimmune encephalitis and antibody-based diagnostics.

Epidemiologic data on neuronal surface antibody (NSAb)-associated autoimmune encephalitides (NSAE) are scarce and heterogeneous. We review our 13-year-long biobank-data collection and provide the incidence of NSAE in two Italian provinces (approx. Population of 1,400,000) over a 5-year period (July 2013-June 2018). NSAbs were diagnosed in 75 out of 1179 tested patients (6.4%). The most common NSAbs were anti-LGI1 (30 cases), followed by NMDAR (24). Eleven cases of NSAE were diagnosed in Treviso and Trento provinces with an estimated incidence of 1.54 per 1,000,000 population (LGI1-encephalitis 0.84; C.I. 0.38-1.88). LGI1-E is the most frequent NSAE among adults.

Prognostic Value of a Combination of Circulating Biomarkers in Critically Ill Patients with Traumatic Brain Injury: Results from the European CREACTIVE Study.

Individualized patient care is essential to reduce the global burden of traumatic brain injury (TBI). This pilot study focused on TBI patients admitted to intensive care units (ICUs) and aimed at identifying patterns of circulating biomarkers associated with the disability level at 6 months from injury, measured by the extended Glasgow Outcome Scale (GOS-E). The concentration of 107 biomarkers, including proteins related to inflammation, innate immunity, TBI, and central nervous system, were quantified in blood samples collected on ICU admission from 80 patients. Patients were randomly selected among those prospectively enrolled in the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) observational study. Six biomarkers were selected to be associated with indicators of primary or secondary brain injury: three glial proteins (glial cell-derived neurotrophic factor, glial fibrillary acidic protein, and S100 calcium-binding protein B) and three cytokines (stem cell factor, fibroblast growth factor [FGF] 23 and FGF19). The subjects were grouped into three clusters according to the expression of these proteins. The distribution of the 6-month GOS-E was significantly different across clusters (p < 0.001). In two clusters, the number of 6-month deaths or vegetative states was significantly lower than expected, as calculated according to a customization of the corticosteroid randomization after significant head injury (CRASH) scores (observed/expected [O/E] events = 0.00, 95% confidence interval [CI]: 0.00-0.90 and 0.00, 95% CI: 0.00-0.94). In one cluster, less-than-expected unfavorable outcomes (O/E = 0.50, 95% CI: 0.05-0.95) and more-than-expected good recoveries (O/E = 1.55, 95% CI: 1.05-2.06) were observed. The improved prognostic accuracy of the pattern of these six circulating biomarkers at ICU admission upon established clinical parameters and computed tomography results needs validation in larger, independent cohorts. Nonetheless, the results of this pilot study are promising and will prompt further research in personalized medicine for TBI patients.

Hospitals with and without neurosurgery: a comparative study evaluating the outcome of patients with traumatic brain injury.

BACKGROUND: We leveraged the data of the international CREACTIVE consortium to investigate whether the outcome of traumatic brain injury (TBI) patients admitted to intensive care units (ICU) in hospitals without on-site neurosurgical capabilities (no-NSH) would differ had the same patients been admitted to ICUs in hospitals with neurosurgical capabilities (NSH). METHODS: The CREACTIVE observational study enrolled more than 8000 patients from 83 ICUs. Adult TBI patients admitted to no-NSH ICUs within 48 h of trauma were propensity-score matched 1:3 with patients admitted to NSH ICUs. The primary outcome was the 6-month extended Glasgow Outcome Scale (GOS-E), while secondary outcomes were ICU and hospital mortality. RESULTS: A total of 232 patients, less than 5% of the eligible cohort, were admitted to no-NSH ICUs. Each of them was matched to 3 NSH patients, leading to a study sample of 928 TBI patients where the no-NSH and NSH groups were well-balanced with respect to all of the variables included into the propensity score. Patients admitted to no-NSH ICUs experienced significantly higher ICU and in-hospital mortality. Compared to the matched NSH ICU admissions, their 6-month GOS-E scores showed a significantly higher prevalence of upper good recovery for cases with mild TBI and low expected mortality risk at admission, along with a progressively higher incidence of poor outcomes with increased TBI severity and mortality risk. CONCLUSIONS: In our study, centralization of TBI patients significantly impacted short- and long-term outcomes. For TBI patients admitted to no-NSH centers, our results suggest that the least critically ill can effectively be managed in centers without neurosurgical capabilities. Conversely, the most complex patients would benefit from being treated in high-volume, neuro-oriented ICUs.

Multicentre longitudinal study of fluid and neuroimaging BIOmarkers of AXonal injury after traumatic brain injury: the BIO-AX-TBI study protocol.

INTRODUCTION AND AIMS: Traumatic brain injury (TBI) often results in persistent disability, due particularly to cognitive impairments. Outcomes remain difficult to predict but appear to relate to axonal injury. Several new approaches involving fluid and neuroimaging biomarkers show promise to sensitively quantify axonal injury. By assessing these longitudinally in a large cohort, we aim both to improve our understanding of the pathophysiology of TBI, and provide better tools to predict clinical outcome. METHODS AND ANALYSIS: BIOmarkers of AXonal injury after TBI is a prospective longitudinal study of fluid and neuroimaging biomarkers of axonal injury after moderate-to-severe TBI, currently being conducted across multiple European centres. We will provide a detailed characterisation of axonal injury after TBI, using fluid (such as plasma/microdialysate neurofilament light) and neuroimaging biomarkers (including diffusion tensor MRI), which will then be related to detailed clinical, cognitive and functional outcome measures. We aim to recruit at least 250 patients, including 40 with cerebral microdialysis performed, with serial assessments performed twice in the first 10 days after injury, subacutely at 10 days to 6 weeks, at 6 and 12 months after injury. ETHICS AND DISSEMINATION: The relevant ethical approvals have been granted by the following ethics committees: in London, by the Camberwell St Giles Research Ethics Committee; in Policlinico (Milan), by the Comitato Etico Milano Area 2; in Niguarda (Milan), by the Comitato Etico Milano Area 3; in Careggi (Florence), by the Comitato Etico Regionale per la Sperimentazione Clinica della Regione Toscana, Sezione area vasta centro; in Trento, by the Trento Comitato Etico per le Sperimentazioni Cliniche, Azienda Provinciale per i Servizi Sanitari della Provincia autonoma di Trento; in Lausanne, by the Commission cantonale d'éthique de la recherche sur l'être humain; in Ljubljana, by the National Medical Ethics Committee at the Ministry of Health of the Republic of Slovenia. The study findings will be disseminated to patients, healthcare professionals, academics and policy-makers including through presentation at conferences and peer-reviewed publications. Data will be shared with approved researchers to provide further insights for patient benefit. TRIAL REGISTRATION NUMBER: NCT03534154.

PROSAFE: a European endeavor to improve quality of critical care medicine in seven countries.

BACKGROUND: Long-lasting shared research databases are an important source of epidemiological information and can promote comparison between different healthcare services. Here we present PROSAFE, an advanced international research network in intensive care medicine, with the focus on assessing and improving the quality of care. The project involved 343 ICUs in seven countries. All patients admitted to the ICU were eligible for data collection. METHODS: The PROSAFE network collected data using the same electronic case report form translated into the corresponding languages. A complex, multidimensional validation system was implemented to ensure maximum data quality. Individual and aggregate reports by country, region, and ICU type were prepared annually. A web-based data-sharing system allowed participants to autonomously perform different analyses on both own data and the entire database. RESULTS: The final analysis was restricted to 262 general ICUs and 432,223 adult patients, mostly admitted to Italian units, where a research network had been active since 1991. Organization of critical care medicine in the seven countries was relatively similar, in terms of staffing, case mix and procedures, suggesting a common understanding of the role of critical care medicine. Conversely, ICU equipment differed, and patient outcomes showed wide variations among countries. CONCLUSIONS: PROSAFE is a permanent, stable, open access, multilingual database for clinical benchmarking, ICU self-evaluation and research within and across countries, which offers a unique opportunity to improve the quality of critical care. Its entry into routine clinical practice on a voluntary basis is testimony to the success and viability of the endeavor.