METHODOLOGY: A total of 80 adult zebrafish were divided into 4 groups namely control, paraquat-treated, pre-hMT2-treated, and post-hMT2-treated groups. Fish were treated with paraquat intraperitoneally every 3 days for 15 days. hMT2 were injected intracranially on day 0 (pre-treated group) and day 16 (post-treated group). Fish were sacrificed on day 22 and the brains were collected for qPCR, ELISA and immunohistochemistry analysis.
RESULTS: qPCR analysis showed that paraquat treatment down-regulated the expression of genes related to dopamine activity and biosynthesis (dat and th1) and neuroprotective agent (bdnf). Paraquat treatment also up-regulated the expression of the mt2, smtb and proinflammatory genes (il-1α, il-1β, tnf-α and cox-2). hMT2 treatment was able to reverse the effects of paraquat. Lipid peroxidation decreased in the paraquat and pre-hMT2-treated groups. However, lipid peroxidation increased in the post-hMT2-treated group. Paraquat treatment also led to a reduction of dopaminergic neurons while their numbers showed an increase following hMT2 treatment.
CONCLUSION: Paraquat has been identified as one of the pesticides that can cause the death of dopaminergic neurons and affect dopamine biosynthesis. Treatment with exogenous hMT2 could reverse the effects of paraquat in the zebrafish brain.
METHODS: The CRASH-3 trial randomised 9202 patients within 3 h of injury with a GCS score ≤ 12 or intracranial bleeding on CT scan and no significant extracranial bleeding to receive TXA or placebo. We conducted an exploratory analysis of the effects of TXA on all-cause mortality within 24 h of injury and within 28 days, excluding patients with a GCS score of 3 or bilateral unreactive pupils, stratified by severity and country income. We pool data from the CRASH-2 and CRASH-3 trials in a one-step fixed effects individual patient data meta-analysis.
RESULTS: There were 7637 patients for analysis after excluding patients with a GCS score of 3 or bilateral unreactive pupils. Of 1112 deaths, 23.3% were within 24 h of injury (early deaths). The risk of early death was reduced with TXA (112 (2.9%) TXA group vs 147 (3.9%) placebo group; risk ratio [RR] RR 0.74, 95% CI 0.58-0.94). There was no evidence of heterogeneity by severity (p = 0.64) or country income (p = 0.68). The risk of death beyond 24 h of injury was similar in the TXA and placebo groups (432 (11.5%) TXA group vs 421 (11.7%) placebo group; RR 0.98, 95% CI 0.69-1.12). The risk of death at 28 days was 14.0% in the TXA group versus 15.1% in the placebo group (544 vs 568 events; RR 0.93, 95% CI 0.83-1.03). When the CRASH-2 and CRASH-3 trial data were pooled, TXA reduced early death (RR 0.78, 95% CI 0.70-0.87) and death within 28 days (RR 0.88, 95% CI 0.82-0.94).
CONCLUSIONS: Tranexamic acid reduces early deaths in non-moribund TBI patients regardless of TBI severity or country income. The effect of tranexamic acid in patients with isolated TBI is similar to that in polytrauma. Treatment is safe and even severely injured patients appear to benefit when treated soon after injury.
TRIAL REGISTRATION: ISRCTN15088122 , registered on 19 July 2011; NCT01402882 , registered on 26 July 2011.
METHODS: In this cross-sectional study, 101 TBI patients were interviewed using the Structured Clinical Interview for DSM-IV Axis I Disorders to assess the rates of depressive and anxiety disorders after TBI. The association of socio-demographic and clinical factors with depressive and anxiety disorders were determined using Pearson's Chi-Square test.
RESULTS: A total of 25% of TBI patients (n = 25/101) were diagnosed with depressive disorders, of which 15% had major depressive disorder (n = 15/101) and 10% had minor depression (n = 10/101). Fourteen percent of TBI patients had anxiety disorders (n = 14/101), of which post-traumatic stress disorder (PTSD) was the commonest anxiety disorder (9%, n = 9/101). Seven percent of TBI patients (n = 7/101) had comorbid depressive and anxiety disorders. The only factor associated with depressive disorder was the duration of TBI (≥ 1 year) while the only factor associated with anxiety disorder was the mechanism of trauma (assault).
CONCLUSION: Major depressive disorder, minor depression and PTSD are common psychiatric complications of TBI. Clinicians should screen for depressive and anxiety disorders in TBI patients, particularly those with ≥1 year of injury and had sustained TBI from assault.
METHODS: This is a prospective substudy nested within the CRASH-3 trial, a randomised placebo-controlled trial of TXA (loading dose 1 g over 10 min, then 1 g infusion over 8 hours) in patients with isolated head injury. CRASH-3 trial patients were recruited between July 2012 and January 2019. Participants in the current substudy were a subset of trial patients enrolled at 10 hospitals in the UK and 4 in Malaysia, who had at least one CT head scan performed as part of the routine clinical practice within 28 days of randomisation. The primary outcome was the volume of intraparenchymal haemorrhage (ie, contusion) measured on a CT scan done after randomisation. Secondary outcomes were progressive intracranial haemorrhage (post-randomisation CT shows >25% of volume seen on pre-randomisation CT), new intracranial haemorrhage (any haemorrhage seen on post-randomisation CT but not on pre-randomisation CT), cerebral infarction (any infarction seen on any type of brain scan done post-randomisation, excluding infarction seen pre-randomisation) and intracranial haemorrhage volume (intraparenchymal + intraventricular + subdural + epidural) in those who underwent neurosurgical haemorrhage evacuation. We planned to conduct sensitivity analyses excluding patients who were severely injured at baseline. Dichotomous outcomes were analysed using relative risks (RR) or hazard ratios (HR), and continuous outcomes using a linear mixed model.
RESULTS: 1767 patients were included in this substudy. One-third of the patients had a baseline GCS (Glasgow Coma Score) of 3 (n=579) and 24% had unilateral or bilateral unreactive pupils. 46% of patients were scanned pre-randomisation and post-randomisation (n=812/1767), 19% were scanned only pre-randomisation (n=341/1767) and 35% were scanned only post-randomisation (n=614/1767). In all patients, there was no evidence that TXA prevents intraparenchymal haemorrhage expansion (estimate=1.09, 95% CI 0.81 to 1.45) or intracranial haemorrhage expansion in patients who underwent neurosurgical haemorrhage evacuation (n=363) (estimate=0.79, 95% CI 0.57 to 1.11). In patients scanned pre-randomisation and post-randomisation (n=812), there was no evidence that TXA reduces progressive haemorrhage (adjusted RR=0.91, 95% CI 0.74 to 1.13) and new haemorrhage (adjusted RR=0.85, 95% CI 0.72 to 1.01). When patients with unreactive pupils at baseline were excluded, there was evidence that TXA prevents new haemorrhage (adjusted RR=0.80, 95% CI 0.66 to 0.98). In patients scanned post-randomisation (n=1431), there was no evidence of an increase in infarction with TXA (adjusted HR=1.28, 95% CI 0.93 to 1.76). A larger proportion of patients without (vs with) a post-randomisation scan died from head injury (38% vs 19%: RR=1.97, 95% CI 1.66 to 2.34, p<0.0001).
CONCLUSION: TXA may prevent new haemorrhage in patients with reactive pupils at baseline. This is consistent with the results of the CRASH-3 trial which found that TXA reduced head injury death in patients with at least one reactive pupil at baseline. However, the large number of patients without post-randomisation scans and the possibility that the availability of scan data depends on whether a patient received TXA, challenges the validity of inferences made using routinely collected scan data. This study highlights the limitations of using routinely collected scan data to examine the effects of TBI treatments.
TRIAL REGISTRATION NUMBER: ISRCTN15088122.
EVIDENCE ACQUISITION: Qualitative research can better assess human sufferings such as in the case of DAI trauma. While quantitative research can measure many psychometric parameters to assess some aspects of trauma conditions, qualitative research is able to fully reveal the meaning, ramification and experience of TBI trauma. Both care giving and rehabilitation are overwhelmingly demanding; hence , they may complicate the caregivers' stress. However, some positive outcomes also exist.
RESULTS: Caregivers involved in caring and rehabilitation of TBI victims may become mentally traumatized. Posttraumatic recovery of the TBI survivor can enhance the entire family's closeness and bonding as well as improve the mental status of the caregiver.
CONCLUSIONS: A long-term longitudinal study encompassing integrated research is needed to fully understand the traumatic experiences of caregivers. Unless research on TBI or DAI trauma is given its proper attention, the burden of trauma and injury on societies will continue to exacerbate globally.
Methods: A cross-sectional study was conducted in a single center in Malaysia via recruiting care providers of patients with TBI. The modified caregiver strain index (MCSI) questionnaires were utilized to ascertain the level of strain. The demographic data of informal care providers were also obtained. Independent sample t-test, analysis of variance (ANOVA), and a linear regression model were processed for data analysis.
Results: A total of 140 informal care providers were included in the study. More than half of informal care providers claimed to have strain (54.3%). Factors associated with increased strain include receiving tertiary education, being of Chinese background, and employed experience higher strain level. Informal care providers with characteristics such as being single, retired and provided care for 5 years experienced a lower level of strain.
Conclusion: Guidance on integrating the TBI knowledge into practice, assessing the care provider's level of strain regularly and providing supportive measures may aid in supporting informal care providers at risk.
METHODS: This is a prospective observational cohort study conducted in Sarawak General Hospital, Malaysia. Patients 12 years of age and older with mild to severe TBI who had a brain computed tomography (CT) done within eight hours of injury were enrolled in the study. A total of 334 patients were recruited from the 5th of August 2016 until the 8th of March 2018 in Sarawak General Hospital. In all 167 of them were administered with TXA and another 167 of the patients were not. The primary outcome expected is the number of good outcomes in isolated TBI patients given TXA. Good outcome is defined by Glasgow Outcome Score-Extended (GOSE) of five and above. Secondary outcome was clot expansion of an intracranial bleed seen on the first scan that had expanded by 25% or more on any dimension on the second scan.
RESULTS: The TXA did not show significant trend of good outcome in terms of GOSE (p=0.763). However, for moderate and severe acute subdural haemorrhage (SDH) subgroups, there was a significant difference (p=0.042). Clot expansion was present in 14 patients (12.7%) with TXA given and in 54 patients (38.8%) without TXA. The difference was statistically significant (p<0.001). Of the patients who received TXA, there was one case (0.6%) of deep vein thrombosis. Apart from that, TXA showed non-significant trend in reducing mortality (p=0.474).
CONCLUSIONS: Tranexamic acid reduces the rate of clot expansion in TBI by 26.1% (38.8-12.7%) without significantly increasing the risk of a thrombotic event. It can also improve the outcome of moderate and severe TBI patients with acute SDH.
Objective: To investigate the effect of dual-task (dual-motor and dual-cognitive task) conditions on spatiotemporal gait parameters during timed up and go test in children with traumatic brain injury.
Methods and Material: A total of 14 children with traumatic brain injury and 21 typically developing children participated in this case-control study. Functional balance was assessed before the actual testing to predict the risk of falls. Timed up and go test was performed under single-task and dual-task (dual-motor and dual-cognitive task) conditions. Spatiotemporal gait parameters were determined using the APDM Mobility Lab system. The descriptive statistics and t-test were used to analyze demographic characteristics and repeated measure ANOVA test was used to analyze the gait parameters.
Results: Under dual-task (dual-motor and dual-cognitive task) conditions during the timed up and go test, gait performance significantly deteriorated. Furthermore, the total time to complete the timed up and go test, stride velocity, cadence, and step time during turning were significantly different between children with traumatic brain injury and typically developing children.
Conclusions: These findings suggest that gait parameters were compromised under dual-task conditions in children with traumatic brain injury. Dual-task conditions may become a component of gait training to ensure a complete and comprehensive rehabilitation program.