832: AMANTADINE, MODAFINIL, OR STANDARD CARE FOR DISORDERS OF CONSCIOUSNESS AFTER TRAUMATIC BRAIN INJURY

Disorders of consciousness may arise from a wide range of incidents, diseases and conditions, including traumatic brain injury, infection or tumours. With her collaborators, Ms Teresa Grimm, at the Department of Music in Carl von Ossietzky University, Germany, is exploring the existing literature and delivering novel findings on the effect of exposure to music for patients who are living with a condition which results in a loss of consciousness.

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Statistical analysis plan for Early mobilisation by head-up tilt with stepping versus standard care after severe traumatic brain injury – a randomised clinical feasibility trial

10.21203/rs.2.468/v2 ◽

2019 ◽

Author(s):

Christian Gunge Riberholt ◽

Christian Gluud ◽

Janus Christian Jakobsen ◽

Christian Ovesen ◽

Jesper Mehlsen ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Statistical Analysis ◽

Brain Injury ◽

Standard Care ◽

Statistical Analysis Plan ◽

Feasibility Trial ◽

Tilt Test ◽

Early Mobilisation ◽

Head Up Tilt ◽

Head Up Tilt Test

Abstract Background: Early mobilisation on a tilt table with stepping versus standard care may be beneficial for patients with severe brain injury, but data from randomised clinical trials are lacking. Methods: This statistical analysis plan describes the analyses of data collected in a randomised clinical feasibility trial for early mobilisation by head-up tilt with stepping versus standard care after severe traumatic brain injury. Primary feasibility outcomes are the proportion of included participants who were randomised out of all screened patients; the proportion of participants allocated to the experimental intervention who received at least 60% of the planned exercise sessions; and safety outcomes such as severe adverse events and reactions and adverse events and reactions. Exploratory clinical outcomes are suspected unexpected severe adverse reactions; and functional outcomes as assessed by Coma Recovery Scale – Revised at four weeks; Early Functional Ability Scale, and Functional Independence Measure at three months. Exploratory physiological outcomes are electrocardiographic data; mean arterial pressure; and middle cerebral artery blood flow velocity, all obtained during the head-up tilt test. From the first head-up tilt test and five days onwards, a heart rate was measured by continuous electrocardiography. The detailed description includes the statistical analysis including use of multiple imputation and Trial Sequential Analysis. Conclusions: The present statistical analysis plan serves to minimise potential trial reporting bias and selective P hacking and to improve transparency. This feasibility trial will inform design and eventual launching of a larger multicentre randomised clinical trial. Trial registration: ClinicalTrials.gov identifier: NCT02924649. Registered on 3 October 2016.

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Statistical analysis plan for early mobilisation by head-up tilt with stepping versus standard care after severe traumatic brain injury – a randomised clinical feasibility trial

10.21203/rs.2.468/v3 ◽

2019 ◽

Author(s):

Christian Gunge Riberholt ◽

Christian Gluud ◽

Janus Christian Jakobsen ◽

Christian Ovesen ◽

Jesper Mehlsen ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Statistical Analysis ◽

Brain Injury ◽

Adverse Events ◽

Severe Traumatic Brain Injury ◽

Standard Care ◽

Statistical Analysis Plan ◽

Feasibility Trial ◽

Early Mobilisation ◽

Head Up Tilt

Abstract Background: Early mobilisation on a tilt table with stepping versus standard care may be beneficial for patients with severe brain injury, but data from randomised clinical trials are lacking. Methods: This detailed statistical analysis plan describes the analyses of data collected in a randomised clinical feasibility trial for early mobilisation by head-up tilt with stepping versus standard care after severe traumatic brain injury. Primary feasibility outcomes are the proportion of included participants who were randomised out of all screened patients; the proportion of participants allocated to the experimental intervention who received at least 60% of the planned exercise sessions; and safety outcomes such as adverse events and reactions and serious adverse events and reactions. Exploratory clinical outcomes are suspected unexpected serious adverse reactions; and functional outcomes as assessed by Coma Recovery Scale – Revised at four weeks; Early Functional Ability Scale and Functional Independence Measure at three months. The description includes the statistical analyses including use of multiple imputation and Trial Sequential Analysis. Conclusions: The present statistical analysis plan serves to minimise potential trial reporting bias and selective P hacking and to improve transparency. This trial will inform the feasibility of a potential future multicentre randomised clinical trial. Trial registration: ClinicalTrials.gov identifier: NCT02924649. Registered on 3 October 2016.

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Therapeutic hypothermia to reduce intracranial pressure after traumatic brain injury: the Eurotherm3235 RCT

Health Technology Assessment ◽

10.3310/hta22450 ◽

2018 ◽

Vol 22 (45) ◽

pp. 1-134 ◽

Cited By ~ 7

Author(s):

Peter JD Andrews ◽

H Louise Sinclair ◽

Aryelly Rodríguez ◽

Bridget Harris ◽

Jonathan Rhodes ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Intracranial Pressure ◽

Mortality Rate ◽

Adverse Events ◽

Technology Assessment ◽

Standard Care ◽

Health Technology ◽

Treatment Allocation ◽

Hypothermia Group

Background Traumatic brain injury (TBI) is a major cause of disability and death in young adults worldwide. It results in around 1 million hospital admissions annually in the European Union (EU), causes a majority of the 50,000 deaths from road traffic accidents and leaves a further ≈10,000 people severely disabled. Objective The Eurotherm3235 Trial was a pragmatic trial examining the effectiveness of hypothermia (32–35 °C) to reduce raised intracranial pressure (ICP) following severe TBI and reduce morbidity and mortality 6 months after TBI. Design An international, multicentre, randomised controlled trial. Setting Specialist neurological critical care units. Participants We included adult participants following TBI. Eligible patients had ICP monitoring in place with an ICP of > 20 mmHg despite first-line treatments. Participants were randomised to receive standard care with the addition of hypothermia (32–35 °C) or standard care alone. Online randomisation and the use of an electronic case report form (CRF) ensured concealment of random treatment allocation. It was not possible to blind local investigators to allocation as it was obvious which participants were receiving hypothermia. We collected information on how well the participant had recovered 6 months after injury. This information was provided either by the participant themself (if they were able) and/or a person close to them by completing the Glasgow Outcome Scale – Extended (GOSE) questionnaire. Telephone follow-up was carried out by a blinded independent clinician. Interventions The primary intervention to reduce ICP in the hypothermia group after randomisation was induction of hypothermia. Core temperature was initially reduced to 35 °C and decreased incrementally to a lower limit of 32 °C if necessary to maintain ICP at < 20 mmHg. Rewarming began after 48 hours if ICP remained controlled. Participants in the standard-care group received usual care at that centre, but without hypothermia. Main outcome measures The primary outcome measure was the GOSE [range 1 (dead) to 8 (upper good recovery)] at 6 months after the injury as assessed by an independent collaborator, blind to the intervention. A priori subgroup analysis tested the relationship between minimisation factors including being aged < 45 years, having a post-resuscitation Glasgow Coma Scale (GCS) motor score of < 2 on admission, having a time from injury of < 12 hours and patient outcome. Results We enrolled 387 patients from 47 centres in 18 countries. The trial was closed to recruitment following concerns raised by the Data and Safety Monitoring Committee in October 2014. On an intention-to-treat basis, 195 participants were randomised to hypothermia treatment and 192 to standard care. Regarding participant outcome, there was a higher mortality rate and poorer functional recovery at 6 months in the hypothermia group. The adjusted common odds ratio (OR) for the primary statistical analysis of the GOSE was 1.54 [95% confidence interval (CI) 1.03 to 2.31]; when the GOSE was dichotomised the OR was 1.74 (95% CI 1.09 to 2.77). Both results favoured standard care alone. In this pragmatic study, we did not collect data on adverse events. Data on serious adverse events (SAEs) were collected but were subject to reporting bias, with most SAEs being reported in the hypothermia group. Conclusions In participants following TBI and with an ICP of > 20 mmHg, titrated therapeutic hypothermia successfully reduced ICP but led to a higher mortality rate and worse functional outcome. Limitations Inability to blind treatment allocation as it was obvious which participants were randomised to the hypothermia group; there was biased recording of SAEs in the hypothermia group. We now believe that more adequately powered clinical trials of common therapies used to reduce ICP, such as hypertonic therapy, barbiturates and hyperventilation, are required to assess their potential benefits and risks to patients. Trial registration Current Controlled Trials ISRCTN34555414. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 45. See the NIHR Journals Library website for further project information. The European Society of Intensive Care Medicine supported the pilot phase of this trial.

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Resting-State Electroencephalography for Prognosis in Disorders of Consciousness Following Traumatic Brain Injury

Frontiers in Neurology ◽

10.3389/fneur.2020.586945 ◽

2020 ◽

Vol 11 ◽

Author(s):

Ruth Pauli ◽

Alice O'Donnell ◽

Damian Cruse

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Resting State ◽

Disorders Of Consciousness ◽

Alpha Power ◽

Disorder Of Consciousness ◽

Term Care ◽

Prognostic Utility ◽

Eeg Recordings

Although the majority of patients recover consciousness after a traumatic brain injury (TBI), a minority develop a prolonged disorder of consciousness, which may never fully resolve. For these patients, accurate prognostication is essential to treatment decisions and long-term care planning. In this review, we evaluate the use of resting-state electroencephalography (EEG) as a prognostic measure in disorders of consciousness following TBI. We highlight that routine clinical EEG recordings have prognostic utility in the short to medium term. In particular, measures of alpha power and variability are indicative of relatively better functional outcomes within the first year post-TBI. This is hypothesized to reflect intact thalamocortical loops, and thus the potential for recovery of consciousness even in the apparent absence of current consciousness. However, there is a lack of research into the use of resting-state EEG for predicting longer-term recovery following TBI. We conclude that, given the potential for patients to demonstrate improvements in consciousness and functional capacity even years after TBI, a research focus on EEG-augmented prognostication in very long-term disorders of consciousness is now required.

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