Low-dose short infusion ketamine as adjunct to morphine for acute long bone fracture in the emergency department: a randomized controlled trial.

BACKGROUND: Ketamine is recognized as an alternative for pain management; however, concerns about emergent adverse reactions have limited its widespread adoption. This study aimed to assess the efficacy of a short infusion of low-dose ketamine (LDK) compared to intravenous morphine (MOR) as adjunctive analgesia for acute long bone fracture pain. METHODS: This single-blinded, randomized controlled trial was conducted in a single emergency department. Patients with acute long bone fractures and numerical rating scale (NRS) pain scores ≥ 6 following an initial dose of intravenous morphine were assigned to receive either a LDK (0.3 mg/kg) over 15 min or intravenous MOR at a dose of 0.1 mg/kg administered over 5 min. Throughout a 120-min observation period, patients were regularly evaluated for pain level (0-10), side effects, and the need for additional rescue analgesia. RESULTS: A total of 58 subjects participated, with 27 in the MOR group and 31 in the LDK group. Demographic variables and baseline NRS scores were comparable between the MOR (8.3 ± 1.3) and LDK (8.9 ± 1.2) groups. At 30 min, the LDK group showed a significantly greater mean reduction in NRS scores (3.1 ± 2.03) compared to the MOR group (1.8 ± 1.59) (p = 0.009). Similarly, at 60 min, there were significant differences in mean NRS score reductions (LDK 3.5 ± 2.17; MOR mean reduction = 2.4, ± 1.84) with a p-value of 0.04. No significant differences were observed at other time intervals. The incidence of dizziness was higher in the LDK group at 19.4% (p = 0.026). CONCLUSION: Short infusion low-dose ketamine, as an adjunct to morphine, is effective in reducing pain during the initial 30 to 60 min and demonstrated comparability to intravenous morphine alone in reducing pain over the subsequent 60 min for acute long bone fractures. However, it was associated with a higher incidence of dizziness. TRIAL REGISTRATION: NMRR17318438970 (2 May 2018; www.nmrr.gov.my ).

Development of a prediction model for emergency medical service witnessed traumatic out-of-hospital cardiac arrest: A multicenter cohort study.

BACKGROUND/PURPOSE: To develop a prediction model for emergency medical technicians (EMTs) to identify trauma patients at high risk of deterioration to emergency medical service (EMS)-witnessed traumatic cardiac arrest (TCA) on the scene or en route. METHODS: We developed a prediction model using the classical cross-validation method from the Pan-Asia Trauma Outcomes Study (PATOS) database from 1 January 2015 to 31 December 2020. Eligible patients aged ≥18 years were transported to the hospital by the EMS. The primary outcome (EMS-witnessed TCA) was defined based on changes in vital signs measured on the scene or en route. We included variables that were immediately measurable as potential predictors when EMTs arrived. An integer point value system was built using multivariable logistic regression. The area under the receiver operating characteristic (AUROC) curve and Hosmer-Lemeshow (HL) test were used to examine discrimination and calibration in the derivation and validation cohorts. RESULTS: In total, 74,844 patients were eligible for database review. The model comprised five prehospital predictors: age <40 years, systolic blood pressure <100 mmHg, respiration rate >20/minute, pulse oximetry <94%, and levels of consciousness to pain or unresponsiveness. The AUROC in the derivation and validation cohorts was 0.767 and 0.782, respectively. The HL test revealed good calibration of the model (p = 0.906). CONCLUSION: We established a prediction model using variables from the PATOS database and measured them immediately after EMS personnel arrived to predict EMS-witnessed TCA. The model allows prehospital medical personnel to focus on high-risk patients and promptly administer optimal treatment.

Characteristic of school injuries in Asia: a cross-national, multi-center observational study.

BACKGROUND: To prevent school injuries, thorough epidemiological data is an essential foundation. We aimed to investigate the characteristics of school injuries in Asia and explore risk factors for major trauma. METHODS: This retrospective study was conducted in the participating centers of the Pan-Asian Trauma Outcome Study from October 2015 to December 2020. Subjects who reported "school" as the site of injury were included. Major trauma was defined as an Injury Severity Score (ISS) value of ≥16. RESULTS: In total, 1305 injury cases (1.0% of 127,715 events) occurred at schools. Among these, 68.2% were children. Unintentional injuries were the leading cause and intentional injuries comprised 7.5% of the cohort. Major trauma accounted for 7.1% of those with documented ISS values. Multivariable regression revealed associations between major trauma and factors, including age, intention of injury (self-harm), type of injury (traffic injuries, falls), and body part injured (head, thorax, and abdomen). Twenty-two (1.7%) died, with six deaths related to self-harm. Females represented 28.4% of injuries but accounted for 40.9% of all deaths. CONCLUSIONS: In Asia, injuries at schools affect a significant number of children. Although the incidence of injuries was higher in males, self-inflicted injuries and mortality cases were relatively higher in females. IMPACT: Epidemiological data and risk factors for major trauma resulting from school injuries in Asia are lacking. This study identified significant risk factors for major trauma occurring at schools, including age, intention of injury (self-harm), injury type (traffic injuries, falls), and body part injured (head, thoracic, and abdominal injuries). Although the incidence of injuries was higher in males, the incidence of self-harm injuries and mortality rates were higher in females. The results of this would make a significant contribution to the development of prevention strategies and relative policies concerning school injuries.

Comparison of on-scene Glasgow Coma Scale with GCS-motor for prediction of 30-day mortality and functional outcomes of patients with trauma in Asia.

BACKGROUND AND IMPORTANCE: This study compared the on-scene Glasgow Coma Scale (GCS) and the GCS-motor (GCS-M) for predictive accuracy of mortality and severe disability using a large, multicenter population of trauma patients in Asian countries. OBJECTIVE: To compare the ability of the prehospital GCS and GCS-M to predict 30-day mortality and severe disability in trauma patients. DESIGN: We used the Pan-Asia Trauma Outcomes Study registry to enroll all trauma patients >18 years of age who presented to hospitals via emergency medical services from 1 January 2016 to November 30, 2018. SETTINGS AND PARTICIPANTS: A total of 16,218 patients were included in the analysis of 30-day mortality and 11 653 patients in the analysis of functional outcomes. OUTCOME MEASURES AND ANALYSIS: The primary outcome was 30-day mortality after injury, and the secondary outcome was severe disability at discharge defined as a Modified Rankin Scale (MRS) score ≥4. Areas under the receiver operating characteristic curve (AUROCs) were compared between GCS and GCS-M for these outcomes. Patients with and without traumatic brain injury (TBI) were analyzed separately. The predictive discrimination ability of logistic regression models for outcomes (30-day mortality and MRS) between GCS and GCS-M is illustrated using AUROCs. MAIN RESULTS: The primary outcome for 30-day mortality was 1.04% and the AUROCs and 95% confidence intervals for prediction were GCS: 0.917 (0.887-0.946) vs. GCS-M:0.907 (0.875-0.938), P  = 0.155. The secondary outcome for poor functional outcome (MRS ≥ 4) was 12.4% and the AUROCs and 95% confidence intervals for prediction were GCS: 0.617 (0.597-0.637) vs. GCS-M: 0.613 (0.593-0.633), P  = 0.616. The subgroup analyses of patients with and without TBI demonstrated consistent discrimination ability between the GCS and GCS-M. The AUROC values of the GCS vs. GCS-M models for 30-day mortality and poor functional outcome were 0.92 (0.821-1.0) vs. 0.92 (0.824-1.0) ( P  = 0.64) and 0.75 (0.72-0.78) vs. 0.74 (0.717-0.758) ( P  = 0.21), respectively. CONCLUSION: In the prehospital setting, on-scene GCS-M was comparable to GCS in predicting 30-day mortality and poor functional outcomes among patients with trauma, whether or not there was a TBI.

Modified physiologic criteria for the field triage scheme: Efficacy of major trauma recognition in different age groups in Asia.

BACKGROUND: Major trauma is a leading cause of unexpected death globally, with increasing age-adjusted death rates for unintentional injuries. Field triage schemes (FTSs) assist emergency medical technicians in identifying appropriate medical care facilities for patients. While full FTSs may improve sensitivity, step-by-step field triage is time-consuming. A simplified FTS (sFTS) that uses only physiological and anatomical criteria may offer a more rapid decision-making process. However, evidence for this approach is limited, and its performance in identifying all age groups requiring trauma center resources in Asia remains unclear. METHODS: We conducted a multinational retrospective cohort study involving adult trauma patients admitted to emergency departments in the included countries from 2016 to 2020. Prehospital and hospital data were reviewed from the Pan-Asia Trauma Outcomes Study database. Patients aged ≥18 years transported by emergency medical services were included. Patients lacking data regarding age, sex, physiological criteria, or injury severity scores were excluded. We examined the performance of sFTS in all age groups and fine-tuned physiological criteria to improve sFTS performance in identifying high-risk trauma patients in different age groups. RESULTS: The sensitivity and specificity of the physiological and anatomical criteria for identifying major trauma (injury severity score ≥ 16) were 80.6% and 58.8%, respectively. The modified sFTS showed increased sensitivity and decreased specificity, with more pronounced changes in the young age group. Adding the shock index further increased sensitivity in both age groups. CONCLUSIONS: sFTS using only physiological and anatomical criteria is suboptimal for Asian adult patients with trauma of all age groups. Adjusting the physiological criteria and adding a shock index as a triage tool can improve the sensitivity of severely injured patients, particularly in young age groups. A swift field triage process can maintain acceptable sensitivity and specificity in severely injured patients.

Analysis of Trauma Characteristics Between the Older and Younger Adult Patient from the Pan Asian Trauma Outcome Study Registry (PATOS).

OBJECTIVE: Asia is experiencing a demographic shift toward an aging population at an unrivaled rate. This can influence the characteristics and outcomes of trauma. We aim to examine different characteristics of older adult trauma patients compared to younger adult trauma patients and describe factors that affect the outcomes in Asian countries. METHODS: This is a retrospective, international, multicenter study of trauma across participating centers in the Pan Asian Trauma Outcome Study (PATOS) registry, which included trauma cases aged ≥18 years, brought to the emergency department (ED) by emergency medical services (EMS) from October 2015 to November 2018. Data of older adults (≥65 years) and younger adults (<65 years) were analyzed and compared. The primary outcome measure was in-hospital mortality, and secondary outcomes were disability at discharge and hospital and intensive care unit (ICU) length of stays. RESULTS: Of 39,804 trauma patients, 10,770 (27.1%) were older adults. Trauma occurred more among older adult women (54.7% vs 33.2%, p < 0.001). Falls were more frequent in older adults (66.3% vs 24.9%, p < 0.001) who also had higher mean Injury Severity Score (ISS) compared to the younger adult trauma patient (5.4 ± 6.78 vs 4.76 ± 8.60, p < 0.001). Older adult trauma patients had a greater incidence of poor Glasgow Outcome Scale (GOS) (13.4% vs 4.1%, p < 0.001), higher hospital mortality (1.5% vs 0.9%, p < 0.001) and longer median hospital length of stay (12.8 vs 9.8, p < 0.001). Multiple logistic regression revealed age (adjusted odds ratio [AOR] 1.06, 95%CI 1.02-1.04, p < 0.001), male sex (AOR 1.60, 95%CI 1.04-2.46, p = 0.032), head and face injuries (AOR 3.25, 95%CI 2.06-5.11, p < 0.001), abdominal and pelvic injuries (AOR 2.78, 95%CI 1.48-5.23, p = 0.002), cardiovascular (AOR 2.71, 95%CI 1.40-5.22, p = 0.003), pulmonary (AOR 3.13, 95%CI 1.30-7.53, p = 0.011) and cancer (AOR 2.03, 95%CI 1.02-4.06, p = 0.045) comorbidities, severe ISS (AOR 2.06, 95%CI 1.23-3.45, p = 0.006), and Glasgow Coma Scale (GCS) ≤8 (AOR 12.50, 95%CI 6.95-22.48, p < 0.001) were significant predictors of hospital mortality. CONCLUSIONS: Older trauma patients in the Asian region have a higher mortality rate than their younger counterparts, with many significant predictors. These findings illustrate the different characteristics of older trauma patients and their potential to influence the outcome. Preventive measures for elderly trauma should be targeted based on these factors.

Characteristics of non-accidental injuries in children and adolescents in Asia: a cross-national, multicenter cohort study.

Children and adolescents are vulnerable to non-accidental injury. Early identification and prevention rely on detailed epidemiological studies, which are limited in Asia. This retrospective study used the registry data of Pan-Asian Trauma Outcome Study (PATOS) from October 1, 2015 to December, 31, 2020. Pediatric patients (aged < 20 years) with non-accidental injuries were enrolled, which were divided by age into preschool (0-6 years), child (7-12 years), and adolescent (13-19 years) groups. Baseline characteristics, injury epidemiology, and excess mortality ratio-adjusted injury severity score (EMR-ISS) were collected. Major trauma was defined as an EMR-ISS score > 24. The study enrolled 451 patients with non-accidental injuries, accounting for 2.81% of pediatric trauma events presented to an emergency department in the PATOS registry. The overall mortality rate was 0.9%, similar to those in Western countries. Mortality rate was high in preschool children (8.7%, p = 0.017) than in other age groups. The sex-specific incidence was higher in boys (3.10% vs. 2.13%, p = 0.001). In adolescents, more events occurred on the street (25.9%), whereas home remained the most common locale in girls of all ages. In the multivariable regression analysis, abdominal and multiple injuries were risk factors for major trauma.

Prediction of Mortality Among Patients With Isolated Traumatic Brain Injury Using Machine Learning Models in Asian Countries: An International Multi-Center Cohort Study.

Abstract Traumatic brain injury (TBI) is a significant healthcare concern in several countries, accounting for a major burden of morbidity, mortality, disability, and socioeconomic losses. Although conventional prognostic models for patients with TBI have been validated, their performance has been limited. Therefore, we aimed to construct machine learning (ML) models to predict the clinical outcomes in adult patients with isolated TBI in Asian countries. The Pan-Asian Trauma Outcome Study registry was used in this study, and the data were prospectively collected from January 1, 2015, to December 31, 2020. Among a total of 6540 patients (≥ 15 years) with isolated moderate and severe TBI, 3276 (50.1%) patients were randomly included with stratification by outcomes and subgrouping variables for model evaluation, and 3264 (49.9%) patients were included for model training and validation. Logistic regression was considered as a baseline, and ML models were constructed and evaluated using the area under the precision-recall curve (AUPRC) as the primary outcome metric, area under the receiver operating characteristic curve (AUROC), and precision at fixed levels of recall. The contribution of the variables to the model prediction was measured using the SHapley Additive exPlanations (SHAP) method. The ML models outperformed logistic regression in predicting the in-hospital mortality. Among the tested models, the gradient-boosted decision tree showed the best performance (AUPRC, 0.746 [0.700-0.789]; AUROC, 0.940 [0.929-0.952]). The most powerful contributors to model prediction were the Glasgow Coma Scale, O2 saturation, transfusion, systolic and diastolic blood pressure, body temperature, and age. Our study suggests that ML techniques might perform better than conventional multi-variate models in predicting the outcomes among adult patients with isolated moderate and severe TBI.

Epidemiology and Prehospital Care of Pediatric Unintentional Injuries Among Countries with Different Economic Status in Asia: A Cross-National, Multi-Center Observational Study.

OBJECTIVE: Injury is a major cause of morbidity and mortality in children. However, the epidemiology and prehospital care for pediatric unintentional injuries in Asia are still unclear. METHODS: A total of 9,737 pediatric patients aged <18 years with unintentional injuries cared for at participating centers of the Pan-Asian Trauma Outcome Study (PATOS) from October 2015 to December 2020 were reviewed retrospectively. Patients were divided into two groups: those <8 and those ≥8 years of age. Variables such as patient demographics, injury epidemiology, Injury Severity Score (ISS), and prehospital care were collected. Injury severity and administered prehospital care stratified by gross national income were also analyzed. RESULTS: Pediatric unintentional injuries accounted for 9.4% of EMS-transported trauma cases in the participating Asian centers, and the mortality rate was 0.88%. The leading cause of injury was traffic injuries in older children aged ≥8 years (56.5%), while falls at home were common among young children aged <8 years (43.9%). Compared with younger children, older children with similar ISS tended to receive more prehospital interventions. Uneven disease severity was found in that older children in lower-middle and upper-middle-income countries had higher ISS compared with those in high-income countries. The performance of prehospital interventions also differed among countries with different gross national incomes. Immobilizations were the most performed prehospital intervention followed by oxygen administration, airway management, and pain control; only one patient received prehospital thoracentesis. Procedures were performed more frequently in high-income countries than in upper-middle-income and lower-middle-income countries. CONCLUSIONS: The major cause of injury was road traffic injuries in older children, while falls at home were common among young children. Prehospital care in pediatric unintentional injuries in Asian countries was not standardized and might be insufficient, and the economic status of countries may affect the implementation of prehospital care.

Association between prehospital fluid resuscitation with crystalloids and outcome of trauma patients in Asia by a cross-national multicenter cohort study.

Prehospital fluid resuscitation with crystalloids in patients following trauma remain controversial. This study aimed to investigate the association between prehospital fluid resuscitation and outcomes of trauma patients in Asia. We conducted a retrospective cohort study of trauma patients between 2016 and 2018 using data from the Pan-Asia Trauma Outcomes Study (PATOS) database. Prehospital fluid resuscitation was defined as any administration of intravenous crystalloid fluid on the ambulance before arrival to hospitals. The outcomes were in-hospital mortality and poor functional outcomes, defined as Modified Rankin Scale ≥ 4. Propensity score matching (PSM) was used to equalize potential prognostic factors in both groups. This study included 31,735 patients from six countries in Asia, and 4318 (13.6%) patients had ever received prehospital fluid resuscitation. The patients receiving prehospital fluid resuscitation had a higher risk of in-hospital mortality, with an adjusted odds ratio (aOR) of 2.02, 95% confidence interval (CI) 1.32-3.10, p = 0.001 in PSM analysis. Prehospital fluid resuscitation was also associated with poor functional outcomes, with an OR 1.73, 95% CI: 1.48-2.03, p < 0.001 in PSM analysis. Prehospital fluid resuscitation in patients with major trauma (injury severity score ≥ 16) presented a higher risk of poor functional outcomes (aOR = 2.65, 95% CI: 1.89-3.73 in PSM analysis, pinteraction = 0.006) via subgroup analysis. Prehospital fluid resuscitation of trauma patients is associated with higher in-hospital mortality and poor functional outcomes in the subgroup in countries studied.

A multicenter cohort study on the association between prehospital immobilization and functional outcome of patients following spinal injury in Asia.

Prehospital spinal immobilization is a widely used procedure in the emergency medical service (EMS) system worldwide, while the incidence of patients with spinal injury (SI) is relatively low, and unnecessary prehospital spinal immobilization is associated with patient complications. This study aimed to determine the association between prehospital spine immobilization and favorable functional outcomes at hospital discharge among trauma patients with SI. We conducted a retrospective cohort study using the Pan-Asia Trauma Outcomes Study (PATOS) registry data from January 1, 2016, to November 30, 2018. A total of 759 patients with SI were enrolled from 43,752 trauma patients in the PATOS registry during the study period. The subjects had a median age of 58 years (Q1-Q3, 41-72), and 438 (57.7%) patients had prehospital spine immobilization. Overall, prehospital spinal immobilization was not associated with favorable functional outcomes at discharge in multivariable logistic regression (aOR 1.06; 95% CI 0.62-1.81, p = 0.826). However, in the subgroup of cervical SI, prehospital spinal immobilization was associated with favorable functional outcomes at discharge (aOR 3.14; 95% CI 1.04-9.50; p = 0.043). Therefore, we suggest that paramedics should be more careful when determining the presence of a cervical SI and should apply full spine immobilization if possible.

Association between the time to definitive care and trauma patient outcomes: every minute in the golden hour matters.

PURPOSE: This study examined the association between lapsed time and trauma patients, suggesting that a shorter time to definitive care leads to a better outcome. METHODS: We used the Pan-Asian Trauma Outcome Study registry to analyze a retrospective cohort of 963 trauma patients who received surgical intervention or transarterial embolization within 2 h of injury in Asian countries between January 2016 and December 2020. Exposure measurement was recorded every 30 min from injury to definitive care. The 30 day mortality rate and functional outcome were studied using the Modified Rankin Scale ratings of 0-3 vs 4-6 for favorable vs poor functional outcomes, respectively. Subgroup analyses of different injury severities and patterns were performed. RESULTS: The mean time from injury to definitive care was 1.28 ± 0.69 h, with cases categorized into the following subgroups: < 30, 30-60, 60-90, and 90-120 min. For all patients, a longer interval was positively associated with the 30 day mortality rate (p = 0.053) and poor functional outcome (p < 0.05). Subgroup analyses showed the same association in the major trauma (n = 321, p < 0.05) and torso injury groups (n = 388, p < 0.01) with the 30 day mortality rate and in the major trauma (p < 0.01), traumatic brain injury (n = 741, p < 0.05), and torso injury (p < 0.05) groups with the poor functional outcome. CONCLUSION: Even within 2 h, a shorter time to definitive care is positively associated with patient survival and functional outcome, especially in the subgroups of major trauma and torso injury.

Association between prehospital field to emergency department delta shock index and in-hospital mortality in patients with torso and extremity trauma: A multinational, observational study.

Hemorrhage, a main cause of mortality in patients with trauma, affects vital signs such as blood pressure and heart rate. Shock index (SI), calculated as heart rate divided by systolic blood pressure, is widely used to estimate the shock status of patients with hemorrhage. The difference in SI between the emergency department and prehospital field can indirectly reflect urgency after trauma. We aimed to determine the association between delta SI (DSI) and in-hospital mortality in patients with torso or extremity trauma. Patients with DSI >0.1 are expected to be associated with high mortality. This retrospective, observational study used data from the Pan-Asian Trauma Outcomes Study. Patients aged 18-85 years with abdomen, chest, upper extremity, lower extremity, or external injury location were included. Patients from China, Indonesia, Japan, Philippines, Thailand, and Vietnam; those who were transferred from another facility; those who were transferred without the use of emergency medical service; those with prehospital cardiac arrest; those with unknown exposure and outcomes were excluded. The exposure and primary outcome were DSI and in-hospital mortality, respectively. The secondary and tertiary outcome was intensive care unit (ICU) admission and massive transfusion, respectively. Multivariate logistic regression analysis was performed to test the association between DSI and outcome. In total, 21,534 patients were enrolled according to the inclusion and exclusion criteria. There were 3,033 patients with DSI >0.1. The in-hospital mortality rate in the DSI >0.1 and ≤0.1 groups was 2.0% and 0.8%, respectively. In multivariate logistic regression analysis, the DSI ≤0.1 group was considered the reference group. The unadjusted and adjusted odds ratios of in-hospital mortality in the DSI >0.1 group were 2.54 (95% confidence interval [CI] 1.88-3.42) and 2.82 (95% CI 2.08-3.84), respectively. The urgency of traumatic hemorrhage can be determined using DSI, which can help hospital staff to provide proper trauma management, such as early trauma surgery or embolization.

Effect of tranexamic acid on intracranial haemorrhage and infarction in patients with traumatic brain injury: a pre-planned substudy in a sample of CRASH-3 trial patients.

BACKGROUND: Early tranexamic acid (TXA) treatment reduces head injury deaths after traumatic brain injury (TBI). We used brain scans that were acquired as part of the routine clinical practice during the CRASH-3 trial (before unblinding) to examine the mechanism of action of TXA in TBI. Specifically, we explored the potential effects of TXA on intracranial haemorrhage and infarction. 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.

Understanding the neuroprotective effect of tranexamic acid: an exploratory analysis of the CRASH-3 randomised trial.

BACKGROUND: The CRASH-3 trial hypothesised that timely tranexamic acid (TXA) treatment might reduce deaths from intracranial bleeding after traumatic brain injury (TBI). To explore the mechanism of action of TXA in TBI, we examined the timing of its effect on death. 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.

Association between prehospital time and outcome of trauma patients in 4 Asian countries: A cross-national, multicenter cohort study.

BACKGROUND: Whether rapid transportation can benefit patients with trauma remains controversial. We determined the association between prehospital time and outcome to explore the concept of the "golden hour" for injured patients. METHODS AND FINDINGS: We conducted a retrospective cohort study of trauma patients transported from the scene to hospitals by emergency medical service (EMS) from January 1, 2016, to November 30, 2018, using data from the Pan-Asia Trauma Outcomes Study (PATOS) database. Prehospital time intervals were categorized into response time (RT), scene to hospital time (SH), and total prehospital time (TPT). The outcomes were 30-day mortality and functional status at hospital discharge. Multivariable logistic regression was used to investigate the association of prehospital time and outcomes to adjust for factors including age, sex, mechanism and type of injury, Injury Severity Score (ISS), Revised Trauma Score (RTS), and prehospital interventions. Overall, 24,365 patients from 4 countries (645 patients from Japan, 16,476 patients from Korea, 5,358 patients from Malaysia, and 1,886 patients from Taiwan) were included in the analysis. Among included patients, the median age was 45 years (lower quartile [Q1]-upper quartile [Q3]: 25-62), and 15,498 (63.6%) patients were male. Median (Q1-Q3) RT, SH, and TPT were 20 (Q1-Q3: 12-39), 21 (Q1-Q3: 16-29), and 47 (Q1-Q3: 32-60) minutes, respectively. In all, 280 patients (1.1%) died within 30 days after injury. Prehospital time intervals were not associated with 30-day mortality. The adjusted odds ratios (aORs) per 10 minutes of RT, SH, and TPT were 0.99 (95% CI 0.92-1.06, p = 0.740), 1.08 (95% CI 1.00-1.17, p = 0.065), and 1.03 (95% CI 0.98-1.09, p = 0.236), respectively. However, long prehospital time was detrimental to functional survival. The aORs of RT, SH, and TPT per 10-minute delay were 1.06 (95% CI 1.04-1.08, p < 0.001), 1.05 (95% CI 1.01-1.08, p = 0.007), and 1.06 (95% CI 1.04-1.08, p < 0.001), respectively. The key limitation of our study is the missing data inherent to the retrospective design. Another major limitation is the aggregate nature of the data from different countries and unaccounted confounders such as in-hospital management. CONCLUSIONS: Longer prehospital time was not associated with an increased risk of 30-day mortality, but it may be associated with increased risk of poor functional outcomes in injured patients. This finding supports the concept of the "golden hour" for trauma patients during prehospital care in the countries studied.

Comparison of trauma systems in Asian countries: a cross-sectional study.

OBJECTIVE: This study aimed to compare the demographic characteristics and trauma service structures and processes of hospitals in 15 countries across the Asia Pacific, and to provide baseline data for the integrated trauma database: the Pan-Asian Trauma Outcomes Study (PATOS). METHODS: Medical directors and emergency physicians at PATOS-participating hospitals in countries across the Asia Pacific were surveyed through a standardized questionnaire. General information, trauma care system data, and trauma emergency department (ED) outcomes at each hospital were collected by email and analyzed using descriptive statistics. RESULTS: Survey data from 35 hospitals across 15 countries were collected from archived data between June 2014 and July 2015. Designated trauma centers were identified as the highest hospital level for trauma patients in 70% of surveyed countries. Half of the hospitals surveyed had special teams for trauma care, and almost all prepared activation protocol documents for these teams. Most hospitals offered specialized trauma education programs, and 72.7% of hospitals had a hospital-based trauma registry. The total number of trauma patients visiting the ED across 25 of the hospitals was 300,376. The overall survival-to-discharge rate was 97.2%; however, it varied greatly between 85.1% and 99.7%. The difference between survival-to-discharge rates of moderate and severe injury groups was highest in Taiwan (41.8%) and lowest in Thailand (18.6%). CONCLUSION: Trauma care systems and ED outcomes vary widely among surveyed hospitals and countries. This information is useful to build further detailed, systematic platforms for trauma surveillance and evidence-based trauma care policies.

Pan-Asian Trauma Outcomes Study (PATOS): Rationale and Methodology of an International and Multicenter Trauma Registry.

BACKGROUND: Trauma is a major health burden and a time-dependent critical emergency condition among developing and developed countries. In Asia, trauma has become a rapidly expanding epidemic and has spread out to many underdeveloped and developing countries through rapid urbanization and industrialization. Most casualties of severe trauma, which results in significant mortality and disability are assessed and transported by prehospital providers including physicians, professional providers, and volunteer providers. Trauma registries have been developed in mostly developed countries and measure care quality, process, and outcomes. In general, existing registries tend to focus on inhospital care rather than prehospital care. METHODS: The Pan-Asia Trauma Outcomes Study (PATOS) was proposed in 2013 and initiated in November, 2015 in order to establish a collaborative standardized study to measure the capabilities, processes and outcomes of trauma care throughout Asia. The PATOS is an international, multicenter, and observational research network to collect trauma cases transported by emergency medical services (EMS) providers. Data are collected from the participating hospital emergency departments in various countries in Asia which receive trauma patients from EMS. Data variables collected include 1) injury epidemiologic factors, 2) EMS factors, 3) emergency department care factors, 4) hospital care factors, and 5) trauma system factors. The authors expect to achieve a sample size of 67,230 cases over the next 2 years of data collection to analyze the association between potential risks and outcomes of trauma. CONCLUSION: The PATOS network is expected to provide comparison of the trauma EMS systems and to benchmark best practice with participating communities.

A retrospective review of paediatric head injuries in Asia - a Pan Asian Trauma Outcomes Study (PATOS) collaboration.

OBJECTIVE: We aim to examine the mechanisms of head-injured children presenting to participating centres in the Pan Asian Trauma Outcomes Study (PATOS) and to evaluate the association between mechanism of injury and severe outcomes. DESIGN AND SETTING: We performed a retrospective review of medical records among emergency departments (EDs) of eight PATOS centres, from September 2014 - August 2015. PARTICIPANTS: We included children <16 years old who presented within 24 hours of head injury and were admitted for observation or required a computed tomography (CT) of the brain from the ED. We excluded children with known coagulopathies, neurological co-morbidities or prior neurosurgery. We reviewed the mechanism, intent, location and object involved in each injury, and the patients' physical findings on presentation. OUTCOMES: Primary outcomes were death, endotracheal intubation or neurosurgical intervention. Secondary outcomes included hospital and ED length of stay. RESULTS: 1438 children were analysed. 953 children (66.3%) were male and the median age was 5.0 years (IQR 1.0-10.0). Falls predominated especially among children younger than 2 years (82.9%), while road traffic injuries were more likely to occur among children 2 years and above compared with younger children (25.8% vs 11.1%). Centres from upper and lower middle-income countries were more likely to receive head injured children from road traffic collisions compared with those from high-income countries (51.4% and 40.9%, vs 10.9%, p<0.0001) and attended to a greater proportion of children with severe outcomes (58.2% and 28.4%, vs 3.6%, p<0.0001). After adjusting for age, gender, intent of injury and gross national income, traffic injuries (adjusted OR 2.183, 95% CI 1.448 to 3.293) were associated with severe outcomes, as compared with falls. CONCLUSIONS: Among children with head injuries, traffic injuries are independently associated with death, endotracheal intubation and neurosurgery. This collaboration among Asian centres holds potential for future prospective childhood injury surveillance.