Does access to acute intensive trauma rehabilitation (AITR) programs affect the disposition of brain injury patients?

Early incorporation of rehabilitation services for severe traumatic brain injury (TBI) patients is expected to improve outcomes and quality of life. This study aimed to compare the outcomes regarding the discharge destination and length of hospital stay of selected TBI patients before and after launching an acute intensive trauma rehabilitation (AITR) program at King Saud Medical City. It was a retrospective observational before-and-after study of TBI patients who were selected and received AITR between December 2018 and December 2019. Participants' demographics, mechanisms of injury, baseline characteristics, and outcomes were compared with TBI patients who were selected for rehabilitation care in the pre-AITR period between August 2017 and November 2018. A total of 108 and 111 patients were managed before and after the introduction of the AITR program, respectively. In the pre-AITR period, 63 (58.3%) patients were discharged home, compared to 87 (78.4%) patients after AITR (p = 0.001, chi-squared 10.2). The pre-AITR group's time to discharge from hospital was 52.4 (SD 30.4) days, which improved to 38.7 (SD 23.2) days in the AITR (p < 0.001; 95% CI 6.6-20.9) group. The early integration of AITR significantly reduced the percentage of patients referred to another rehabilitation or long-term facility. We also emphasize the importance of physical medicine and rehabilitation (PM&R) specialists as the coordinators of structured, comprehensive, and holistic rehabilitation programs delivered by the multi-professional team working in an interdisciplinary way. The leadership and coordination of the PM&R physicians are likely to be effective, especially for those with severe disabilities after brain injury.

Efficacy of high-dose versus low-dose vitamin D supplementation on serum levels of inflammatory factors and mortality rate in severe traumatic brain injury patients: study protocol for a randomized placebo-controlled trial.

BACKGROUND: Traumatic brain injury (TBI) is the most common trauma worldwide and is a leading cause of injury-related death and disability. Inflammation is initiated as a result of the TBI, which is in association with severity of illness and mortality in brain trauma patients, especially in subdural hemorrhage and epidural hemorrhage cases. A high percentage of adults admitted to the intensive care unit with TBI are diagnosed with vitamin D deficiency; this deficiency may induce impaired immune responses and increase the risk of infections. Vitamin D intervention has been shown to modulate pro- and anti-inflammatory cytokines in non-critically ill patients, but to date, there is no substantial data on the effectiveness of vitamin D for the improvement of immune function in traumatic brain injury patients. METHODS/DESIGN: A randomized clinical trial (RCT) will be performed on 74 Iranian adults 18-65 years old with brain trauma and will be treated daily with vitamin D supplements (100,000 IU oral drop) or a similar placebo (1000 IU) for 5 days. DISCUSSION: If this randomized clinical trial demonstrates reductions in inflammatory cytokines, it would provide evidence for a multicenter clinical trial to evaluate the efficacy of vitamin D supplementation in neurocritically ill patients. Since vitamin D supplements are inexpensive and safe, this clinical trial could have the potential to improve clinical outcomes in traumatic brain injury patients through reduction of inflammation and infection-associated morbidity and mortality rates. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT20180619040151N3 . Registered on 10 August 2019.

A meta-analysis of the effects of therapeutic hypothermia in adult patients with traumatic brain injury.

PURPOSE: Therapeutic hypothermia management remains controversial in patients with traumatic brain injury. We conducted a meta-analysis to evaluate the risks and benefits of therapeutic hypothermia management in patients with traumatic brain injury. METHODS: We searched the Web of Science, PubMed, Embase, Cochrane (Central) and Clinical Trials databases from inception to January 17, 2019. Eligible studies were randomised controlled trials that investigated therapeutic hypothermia management versus normothermia management in patients with traumatic brain injury. We collected the individual data of the patients from each included study. Meta-analyses were performed for 6-month mortality, unfavourable functional outcome and pneumonia morbidity. The risk of bias was evaluated using the Cochrane Risk of Bias tool. RESULTS: Twenty-three trials involving a total of 2796 patients were included. The randomised controlled trials with a high quality show significantly more mortality in the therapeutic hypothermia group [risk ratio (RR) 1.26, 95% confidence interval (CI) 1.04 to 1.53, p = 0.02]. Lower mortality in the therapeutic hypothermia group occurred when therapeutic hypothermia was received within 24 h (RR 0.83, 95% CI 0.71 to 0.96, p = 0.01), when hypothermia was received for treatment (RR 0.66, 95% CI 0.49 to 0.88, p = 0.006) or when hypothermia was combined with post-craniectomy measures (RR 0.69, 95% CI 0.48 to 1.00, p = 0.05). The risk of unfavourable functional outcome following therapeutic hypothermia management appeared to be significantly reduced (RR 0.78, 95% CI 0.67 to 0.91, p = 0.001). The meta-analysis suggested that there was a significant increase in the risk of pneumonia with therapeutic hypothermia management (RR 1.48, 95% CI 1.11 to 1.97, p = 0.007). CONCLUSIONS: Our meta-analysis demonstrated that therapeutic hypothermia did not reduce but might increase the mortality rate of patients with traumatic brain injury in some high-quality studies. However, traumatic brain injury patients with elevated intracranial hypertension could benefit from hypothermia in therapeutic management instead of prophylaxis when initiated within 24 h.

Is rivaroxaban associated with higher morbidity and mortality in patients with traumatic head injuries? A retrospective cohort study comparing rivaroxaban, no anticoagulation, and phenprocoumon.

OBJECTIVES: The use of new anticoagulants potentially carries the risk of increased intracranial bleeding, but there is a lack of evidence. The aim of this study was to investigate whether the morbidity and mortality differs in head trauma patients depending on the type of anticoagulation. PATIENTS AND METHODS: A retrospective cohort study was conducted in 2009-2014. Based on sex, age, and Glasgow-Coma Scale (GCS), patients that received rivaroxaban were matched to two control groups, one that received no anticoagulant and another one that received phenprocoumon. The primary outcome was mortality. Among others, secondary outcome variables were the length of stay (LOS) at the hospital and presence of an intracranial injury. RESULTS: Sixty-nine patients (23 patients per group) were analyzed. The characteristics of patients did not differ significantly across groups. There were no significant differences between groups for the primary and secondary outcomes. Two patients died in the rivaroxaban group (one of them likely due to head trauma), while one patient died in the phenprocoumon group (likely not due to head trauma), and no patient died in the no anticoagulatoin group (p = 0.36). The LOS at the hospital was similar (5.0, 4.0, and 5.0 days; p = 0.94). An intracranial injury was observed in a similar number of patients in all groups (n = 11, n = 10, and n = 8; p = 0.75). CONCLUSION: Although limited in size, this study did not observe significant outcome differences in patients with traumatic head injuries, who received rivaroxaban, no anticoagulant or phenprocoumon. Although not significant, the only death likely due to head trauma in the study occurred in the rivaroxaban group. Larger studies are needed before clinical application of these findings.

Initiating Nutritional Support Before 72 Hours Is Associated With Favorable Outcome After Severe Traumatic Brain Injury in Children: A Secondary Analysis of a Randomized, Controlled Trial of Therapeutic Hypothermia.

OBJECTIVES: To understand the relationship between the timing of initiation of nutritional support in children with severe traumatic brain injury and outcomes. DESIGN: Secondary analysis of a randomized, controlled trial of therapeutic hypothermia (Pediatric Traumatic Brain Injury Consortium: Hypothermia, also known as "the Cool Kids Trial" (NCT 00222742). SETTINGS: Fifteen clinical sites in the United States, Australia, and New Zealand. SUBJECTS: Inclusion criteria included 1) age less than 18 years, 2) postresuscitation Glasgow Coma Scale less than or equal to 8, 3) Glasgow Coma Scale motor score less than 6, and 4) available to be randomized within 6 hours after injury. Exclusion criteria included normal head CT, Glasgow Coma Scale equals to 3, hypotension for greater than 10 minutes (< fifth percentile for age), uncorrectable coagulopathy, hypoxia (arterial oxygen saturation < 90% for > 30 min), pregnancy, penetrating injury, and unavailability of a parent or guardian to consent at centers without emergency waiver of consent. INTERVENTIONS: Therapeutic hypothermia (32-33°C for 48 hr) followed by slow rewarming for the primary study. For this analysis, the only intervention was the extraction of data regarding nutritional support from the existing database. MEASUREMENTS AND MAIN RESULTS: Timing of initiation of nutritional support was determined and patients stratified into four groups (group 1-no nutritional support over first 7 d; group 2-nutritional support initiated < 48 hr after injury; group 3-nutritional support initiated 48 to < 72 hr after injury; group 4-nutritional support initiated 72-168 hr after injury). Outcomes were also stratified (mortality and Glasgow Outcomes Scale-Extended for Pediatrics; 1-4, 5-7, 8) at 6 and 12 months. Mixed-effects models were performed to define the relationship between nutrition and outcome. Children (n = 90, 77 randomized, 13 run-in) were enrolled (mean Glasgow Coma Scale = 5.8); the mortality rate was 13.3%. 57.8% of subjects received hypothermia Initiation of nutrition before 72 hours was associated with survival (p = 0.01), favorable 6 months Glasgow Outcomes Scale-Extended for Pediatrics (p = 0.03), and favorable 12 months Glasgow Outcomes Scale-Extended for Pediatrics (p = 0.04). Specifically, groups 2 and 3 had favorable outcomes versus group 1. CONCLUSIONS: Initiation of nutritional support before 72 hours after traumatic brain injury was associated with decreased mortality and favorable outcome in this secondary analysis. Although this provides a rationale to initiate nutritional support early after traumatic brain injury, definitive studies that control for important covariates (severity of injury, clinical site, calories delivered, parenteral/enteral routes, and other factors) are needed to provide definitive evidence on the optimization of the timing of nutritional support after severe traumatic brain injury in children.

Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children.

BACKGROUND: There are no therapies shown to improve outcome after severe traumatic brain injury (TBI) in humans, a leading cause of morbidity and mortality. We sought to verify brain exposure of the systemically administered antioxidant N-acetylcysteine (NAC) and the synergistic adjuvant probenecid, and identify adverse effects of this drug combination after severe TBI in children. METHODS: IRB-approved, randomized, double-blind, placebo controlled Phase I study in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit after severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring an externalized ventricular drain for measurement of intracranial pressure (ICP). Patients were recruited from November 2011-August 2013. Fourteen patients (n = 7/group) were randomly assigned after obtaining informed consent to receive probenecid (25 mg/kg load, then 10 mg/kg/dose q6h×11 doses) and NAC (140 mg/kg load, then 70 mg/kg/dose q4h×17 doses), or placebos via naso/orogastric tube. Serum and CSF samples were drawn pre-bolus and 1-96 h after randomization and drug concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS) score was assessed at 3 months. RESULTS: There were no adverse events attributable to drug treatment. One patient in the placebo group was withdrawn due to adverse effects. In the treatment group, NAC concentrations ranged from 16,977.3±2,212.3 to 16,786.1±3,285.3 in serum and from 269.3±113.0 to 467.9±262.7 ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid concentrations ranged from 75.4.3±10.0 to 52.9±25.8 in serum and 5.4±1.0 to 4.6±2.1 µg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean±SEM). Temperature, mean arterial pressure, ICP, use of ICP-directed therapies, surveillance serum brain injury biomarkers, and GOS at 3 months were not different between groups. CONCLUSIONS: Treatment resulted in detectable concentrations of NAC and probenecid in CSF and was not associated with undesirable effects after TBI in children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01322009.

Traumatic Brain Injury-Related Emergency Department Visits, Hospitalizations, and Deaths - United States, 2007 and 2013.

PROBLEM/CONDITION: Traumatic brain injury (TBI) has short- and long-term adverse clinical outcomes, including death and disability. TBI can be caused by a number of principal mechanisms, including motor-vehicle crashes, falls, and assaults. This report describes the estimated incidence of TBI-related emergency department (ED) visits, hospitalizations, and deaths during 2013 and makes comparisons to similar estimates from 2007. REPORTING PERIOD: 2007 and 2013. DESCRIPTION OF SYSTEM: State-based administrative health care data were used to calculate estimates of TBI-related ED visits and hospitalizations by principal mechanism of injury, age group, sex, and injury intent. Categories of injury intent included unintentional (motor-vehicle crashes, falls, being struck by or against an object, mechanism unspecified), intentional (self-harm and assault/homicide), and undetermined intent. These health records come from the Healthcare Cost and Utilization Project's National Emergency Department Sample and National Inpatient Sample. TBI-related death analyses used CDC multiple-cause-of-death public-use data files, which contain death certificate data from all 50 states and the District of Columbia. RESULTS: In 2013, a total of approximately 2.8 million TBI-related ED visits, hospitalizations, and deaths (TBI-EDHDs) occurred in the United States. This consisted of approximately 2.5 million TBI-related ED visits, approximately 282,000 TBI-related hospitalizations, and approximately 56,000 TBI-related deaths. TBIs were diagnosed in nearly 2.8 million (1.9%) of the approximately 149 million total injury- and noninjury-related EDHDs that occurred in the United States during 2013. Rates of TBI-EDHDs varied by age, with the highest rates observed among persons aged ≥75 years (2,232.2 per 100,000 population), 0-4 years (1,591.5), and 15-24 years (1,080.7). Overall, males had higher age-adjusted rates of TBI-EDHDs (959.0) compared with females (810.8) and the most common principal mechanisms of injury for all age groups included falls (413.2, age-adjusted), being struck by or against an object (142.1, age-adjusted), and motor-vehicle crashes (121.7, age-adjusted). The age-adjusted rate of ED visits was higher in 2013 (787.1) versus 2007 (534.4), with fall-related TBIs among persons aged ≥75 years accounting for 17.9% of the increase in the number of TBI-related ED visits. The number and rate of TBI-related hospitalizations also increased among persons aged ≥75 years (from 356.9 in 2007 to 454.4 in 2013), primarily because of falls. Whereas motor-vehicle crashes were the leading cause of TBI-related deaths in 2007 in both number and rate, in 2013, intentional self-harm was the leading cause in number and rate. The overall age-adjusted rate of TBI-related deaths for all ages decreased from 17.9 in 2007 to 17.0 in 2013; however, age-adjusted TBI-related death rates attributable to falls increased from 3.8 in 2007 to 4.5 in 2013, primarily among older adults. Although the age-adjusted rate of TBI-related deaths attributable to motor-vehicle crashes decreased from 5.0 in 2007 to 3.4 in 2013, the age-adjusted rate of TBI-related ED visits attributable to motor-vehicle crashes increased from 83.8 in 2007 to 99.5 in 2013. The age-adjusted rate of TBI-related hospitalizations attributable to motor-vehicle crashes decreased from 23.5 in 2007 to 18.8 in 2013. INTERPRETATION: Progress has been made to prevent motor-vehicle crashes, resulting in a decrease in the number of TBI-related hospitalizations and deaths from 2007 to 2013. However, during the same time, the number and rate of older adult fall-related TBIs have increased substantially. Although considerable public interest has focused on sports-related concussion in youth, the findings in this report suggest that TBIs attributable to older adult falls, many of which result in hospitalization and death, should receive public health attention. PUBLIC HEALTH ACTIONS: The increase in the number of fall-related TBIs in older adults suggests an urgent need to enhance fall-prevention efforts in that population. Multiple effective interventions have been identified, and CDC has developed the STEADI initiative (Stopping Elderly Accidents Deaths and Injuries) as a comprehensive strategy that incorporates empirically supported clinical guidelines and scientifically tested interventions to help primary care providers address their patients' fall risk through the identification of modifiable risk factors and implementation of effective interventions (e.g., exercise, medication management, and Vitamin D supplementation).

Association Between Comorbidities, Nutritional Status, and Anticlotting Drugs and Neurologic Outcomes in Geriatric Patients with Traumatic Brain Injury.

BACKGROUND: Several studies using trauma data banks and registers showed that age, Glasgow Coma Scale (GCS), Injury Severity Score, and intraventricular hemorrhage were independent factors for neurologic outcomes in geriatric patients with traumatic brain injury (TBI). However, these analyses did not comprehensively evaluate factors particularly associated with geriatric patients. We aimed to identify factors particularly associated with geriatric patients that affect neurologic outcomes in TBI. METHODS: Patients aged ≥65 years who were hospitalized consecutively in Kagawa University Hospital with severe TBI between 1 January 2008 and 31 October 2015 were retrospectively reviewed. We evaluated background factors particularly associated with geriatric patients, including comorbidities (Charlson Comorbidity Index [CCI]), nutritional status (serum albumin level), and presence/absence of antiplatelet and anticoagulant drugs, in addition to baseline characteristics. Multivariate analyses were performed to identify independent predictors of unfavorable neurologic outcomes (UO), as defined as a Glasgow Outcome Scale score of 1-3 at discharge from hospital. The association between CCI and UO was evaluated in a subgroup analysis. RESULTS: UO occurred in 65.0% of 140 patients. Multivariate analyses showed that the CCI (odds ratio, 1.91; 95% confidence interval, 1.21-3.29; P = 0.011), age, and GCS were independent predictors of UO. In subgroup analyses of patients with an initial GCS score of 13-15, the rate of UO significantly increased with CCI score (CCI 0, 35.5%; CCI 1 or 2, 39.4%; CCI >2, 83.3%; P < 0.01). CONCLUSIONS: CCI was an independent predictor of UO in geriatric patients with severe TBI.