Geographical Distribution of Neurosurgeons and Emergency Neurosurgical Services in Pakistan.

BACKGROUND AND OBJECTIVE: According to the World Federation of Neurosurgical Societies (WFNS), a minimum neurosurgery workforce density should be 1 per 200,000 population for optimum access to neurosurgical care. Pakistan lags behind in the number of neurosurgeons, and disproportionate geographical distribution further increases disparity. Our objective was to geographically map the density of neurosurgeons and emergency neurosurgical services (ENS) in Pakistan. METHODS: This survey was circulated among 307 neurosurgeons. Data were analyzed using SPSS v21. The number of neurosurgeons and ENS were plotted on the population density map using ArcGIS Pro 3.0.0 software. RESULTS: Three hundred and seven neurosurgeons working at 74 centers responded to our survey (93.3% coverage). The current density of neurosurgeons in Pakistan is 0.14/100,000. The 2 more populous provinces, Punjab and Sindh, have 42.3% (130) and 35.8% (110) neurosurgeons, respectively. They also housed nearly 3 quarters of all the neurosurgery centers in urban districts. Karachi and Lahore accommodate 135 (44%) of all the country's neurosurgeons, having 0.29 and 0.51 neurosurgeons/100,000 respectively. Management of traumatic brain injury is offered at 65 centers (87.8%). Nearly all centers are equipped with computed tomography (CT) scan machine (74; 97%), but magnetic resonance imaging (MRI) facility is available at 55 (72%) centers and 37 (49%) centers have angiography suites. Sixty nine centers (93.2%) have C-arm fluoroscopes available. CONCLUSIONS: The geographical mapping of neurosurgeons and neurosurgical facilities is highly skewed towards urban centers, increasing disparity in access to timely neurosurgical emergency services. Four times more neurosurgeons are required in Pakistan to bridge the gap in neurosurgical workforce.

Stem Cells for Spinal Cord Injury - Are we Closer to Clinical Application in Humans?

Recovery after spinal cord injury (SCI) is highly variable, often leaving the victim disabled for life and having to deal with the complications of paraplegia. Stem cell therapy is a potential hope for these patients. Most of the research on use of stem cells for SCI has been on animal models in laboratories. Some recent clinical trials involving human subjects have shown positive outcomes with regards to tissue growth after transplantation, but meaningful functional recovery is yet to be seen. The emergence of lumbar cord simulation is a new approach and the recent identification of recovery organizing interneurons points to a pathway that could integrate neuromodulation with cellular therapy.

Association of age and severe injury in young motorcycle riders: A cross-sectional study from Karachi, Pakistan.

INTRODUCTION: The burden imposed by motorcyclist deaths and injuries is high in low- and middle-income countries. Many injured motorcycle riders in these settings are underage. The aim of this study was to assess the association between age and severe injury in young motorcycle riders. METHODS: We analysed road traffic injury surveillance data from the emergency rooms of five hospitals in Karachi from 2007 to 2015. We used logistic regression to assess the association of motorcycle riders' age, categorised as underage (13-17 years), early licensing age (18-19 years) and late licensing age (20-24 years), with severe injury, defined as an Injury Severity Score (ISS) ≥ 16. RESULTS: The study sample included 45,366 motorcycle riders. There were 10115 (22.3%) motorcycle riders aged 13-17 years, 9899 (21.8%) aged 18-19 years and 25352 (55.9%) aged 20-24 years. Almost all were male (99%). Being aged 13-17 years (adjusted odds ratio 1.25; 95% CI 1.11, 1.42) and 18-19 years (adjusted odds ratio 1.26; 95% CI 1.10, 1.43) were associated with higher odds of severe injury compared with being aged 20-24 years. CONCLUSION: Motorcycle riders who presented to the hospital with injuries after road traffic crashes and were aged 13-17 years and 18-19 years had significantly higher odds of severe injury than those aged 20-24 years.

Prioritizing Pituitary Adenoma Care in Pakistan: Analysis from an Epidemiological Study.

OBJECTIVE: To identify symptoms and risk factors and promptly diagnose, treat, and manage pituitary adenomas. Prioritizing care for pituitary adenomas will reduce the prolonged disability. Method: Patients with a histopathological diagnosis of a pituitary adenoma that presented at 32 tertiary care neurosurgical centres were included. The information recorded included demographics, treatment methods, adjuvant chemoradiotherapy and loss to follow-up. Data on tumour size, functionality, and laterality were collected. RESULTS: Of the 32 hospitals surveyed, 24 operated on pituitary adenomas, and treated 277 patients. The mean age at diagnosis was 39.8 ± 13 years, with a majority of males (63.5%) being diagnosed than females. Paediatric cases constituted only 4.7% of the total pituitary adenomas operated upon. Gross total resection was reported for 155 (56%) of all pituitary adenoma patients. Majority of the patients affected by pituitary adenomas (80.1%) were from the working class. CONCLUSIONS: Highlighting care for non-malignant brain tumours is important for Pakistan's health system. Evidence pertaining to gender and age disparities indicates that males in the younger age groups are predominantly affected, which takes a large socio-economic toll on patients and their households. This study also highlights the need to incorporate digital health technologies for postoperative follow-up and adjuvant treatment.

Private vs public care for intracranial tumours: Findings from Pakistan.

OBJECTIVE: To observe the patient characteristics and centres providing neuro-oncological care in public and private health hospitals in Pakistan. Method: The Pakistan Association of Neuro-oncology carried out a retrospective, cross-sectional study in 2019 on patients admitted to 32 hospitals in Pakistan, with dedicated neurosurgical facilities. Patients with a histopathological diagnosis of an intracranial tumour were included. RESULTS: Public health care facilities catered for 84% patients with ages between 20 and 60 years and children having intracranial tumours. Private centres were utilised by 66.7% patients from the upper socioeconomic sector. More patients were lost to follow-up in the public sector (n = 784) versus in the private sector (n = 356). Mortality was also higher in the public sector hospitals, (13.9%) as compared to 9.6% in the private sector. CONCLUSIONS: Public and private sector health services for neuro-oncological care in Pakistan still have a long way to go to cover the gaps for unmet needs. Strengthening health systems for brain tumour care is imperative to increase both the access to care and the quality of care to fulfil this need.

Unusual presentation in syndrome of trephined - A unique case observation.

Background: Syndrome of trephined (SoT) is a well-recognized complication of decompressive craniectomy (DC). The understanding of SoT has improved more recently with the increasing utilization of DC for severely raised intracranial pressure. It usually presents after a period of weeks or months with a cluster of adverse neurological symptoms, most commonly with worsening of motor strength. Case Description: An elderly gentleman with traumatic brain injury underwent DC. He later developed a sinking flap and unexplained agitation which responded to cranioplasty by returning to a state of calm. His cognitive function further improved over a period of 6 months. This is an unusual observation reported in this case. Conclusion: Timely recognition of the cognitive complications of craniectomy that may respond to early cranioplasty promises to decrease the length of hospital stay and enhance rehabilitation in such patients.

Third ventricular diverticulum of the suprapineal recess can be a rare and confounding complication of chronic hydrocephalus: A case report with 2-year follow-up.

PURPOSE: Chronic hydrocephalus is rarely seen in developed countries due to the widespread availability of CT scans for diagnosis and early treatment. In developing countries, it is more frequently encountered along with its rare complication of diverticulum formation. METHODS: We report a case of a previously healthy 6 year old girl who presented with a 10 day history of headache, 3 day history of drowsiness and a single episode of generalized tonic clonic seizures. We review the literature on such cases and include imagining studies at follow up. RESULTS: A CT scan done outside our hospital had been reported to be demonstrating a posterior fossa arachnoid cyst with resultant obstructive hydrocephalus. We first placed an external ventricular drain and performed an MRI of the brain to further characterize the lesion. It was again reported as an arachnoid cyst but on further scrutiny it was appreciated that it was in fact a third ventricular diverticulum of the suprapineal recess. She underwent ventriculoperitoneal shunt placement which led to resolution of the hydrocephalus as well as the diverticulum. CONCLUSION: These diverticulae develop secondary to ventricular rupture in the setting of chronic untreated hydrocephalus. This pathology was first described in 1940 and over the years its identification has decreased due to a much lower incidence of chronic untreated hydrocephalus.

Primary trauma care course: Alternative basic trauma course in developing countries. "The Need Of The Hour".

OBJECTIVE: Low- and middle-income countries account for over 90% of all road traffic injury deaths. Despite this, formal training in trauma management is not widely adopted in these countries. No specific training was available in prehospital or emergency department for life support before primary trauma care (PTC) course. This study was conducted to assess the effectiveness of the PTC course in the improvement of knowledge and skills of trauma management among participant in Pakistan. METHOD: Two days of PTC courses were organised and conducted in various regions of Pakistan, participants per course comprising medical students, doctors, house officers, residents, and paramedics. The course comprises lectures of 5 hours and 30 minutes, skills workshops for 3 hours and discussion and multisystem trauma scenarios for 3 hours. Trauma management knowledge and clinical confidence of candidates were assessed using a predetermined multiple-choice questionnaire of 30 MCQs both at pre- and post-course, and using clinical scenarios, confidence matrix was assessed. RESULTS: A total 7852 of participants were trained, an average of 2 courses per month and 302 total courses. Mean score of pre-course MCQs was 60% and mean score of post-course MCQs was 82%. Among the participant postgraduate trainees, average in trauma knowledge and trauma clinical confidence were significantly higher in both pre- and post-course. The mean score of pre-course confidence matrix was 70% and the mean score of post-course confidence matrix was 93%; at the end of course, all participants showed a high level of confidence in managing trauma mock scenarios. A total of 5889 (75%) participants had a ≥78.5% post-workshop knowledge score. However, only 1963 (25%) participants had a trauma skill score with ≤75 marks. CONCLUSION: PTC workshop could be an alternative and cost-effective flexible course for gaining knowledge and clinical skills of initial trauma management and strengthening the capacity of trauma management training in developing countries with minimal resources for saving the life of trauma victims.

Tranexamic acid to reduce head injury death in people with traumatic brain injury: the CRASH-3 international RCT.

BACKGROUND: Tranexamic acid safely reduces mortality in traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury and can cause brain herniation and death. We assessed the effects of tranexamic acid in traumatic brain injury patients. OBJECTIVE: To assess the effects of tranexamic acid on death, disability and vascular occlusive events in traumatic brain injury patients. We also assessed cost-effectiveness. DESIGN: Randomised trial and economic evaluation. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers and those assessing outcomes were masked to allocation. All analyses were by intention to treat. We assessed the cost-effectiveness of tranexamic acid versus no treatment from a UK NHS perspective using the trial results and a Markov model. SETTING: 175 hospitals in 29 countries. PARTICIPANTS: Adults with traumatic brain injury within 3 hours of injury with a Glasgow Coma Scale score of ≤ 12 or any intracranial bleeding on computerised tomography scan, and no major extracranial bleeding, were eligible. INTERVENTION: Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo. MAIN OUTCOME MEASURES: Head injury death in hospital within 28 days of injury in patients treated within 3 hours of injury. Secondary outcomes were early head injury deaths, all-cause and cause-specific mortality, disability, vascular occlusive events, seizures, complications and adverse events. RESULTS: Among patients treated within 3 hours of injury (n = 9127), the risk of head injury death was 18.5% in the tranexamic acid group versus 19.8% in the placebo group (855/4613 vs. 892/4514; risk ratio 0.94, 95% confidence interval 0.86 to 1.02). In a prespecified analysis excluding patients with a Glasgow Coma Scale score of 3 or bilateral unreactive pupils at baseline, the results were 12.5% in the tranexamic acid group versus 14.0% in the placebo group (485/3880 vs. 525/3757; risk ratio 0.89, 95% confidence interval 0.80 to 1.00). There was a reduction in the risk of head injury death with tranexamic acid in those with mild to moderate head injury (166/2846 vs. 207/2769; risk ratio 0.78, 95% confidence interval 0.64 to 0.95), but in those with severe head injury (689/1739 vs. 685/1710; risk ratio 0.99, 95% confidence interval 0.91 to 1.07) there was no apparent reduction (p-value for heterogeneity = 0.030). Early treatment was more effective in mild and moderate head injury (p = 0.005), but there was no obvious impact of time to treatment in cases of severe head injury (p = 0.73). The risk of disability, vascular occlusive events and seizures was similar in both groups. Tranexamic acid is highly cost-effective for mild and moderate traumatic brain injury (base case of £4288 per quality-adjusted life-year gained). CONCLUSION: Early tranexamic acid treatment reduces head injury deaths. Treatment is cost-effective for patients with mild or moderate traumatic brain injury, or those with both pupils reactive. FUTURE WORK: Further trials should examine early tranexamic acid treatment in mild head injury. Research on alternative routes of administration is needed. LIMITATIONS: Time to treatment may have been underestimated. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15088122, ClinicalTrials.gov NCT01402882, EudraCT 2011-003669-14, Pan African Clinical Trial Registry PACTR20121000441277. FUNDING: The 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. 25, No. 26. See the NIHR Journals Library website for further project information. In addition, funding was provided by JP Moulton Charitable Trust, Joint Global Health Trials (Medical Research Council, Department for International Development and the Wellcome Trust). This project was funded by the NIHR Global Health Trials programme.

Traumatic brain injury is a leading cause of death and disability worldwide, with over 60 million new cases each year. When the head is injured there is often bleeding inside the brain, which can continue for some time and worsen after hospital admission. This bleeding increases pressure inside the skull, causing further damage to the brain, which can be fatal or result in serious disability. Tranexamic acid is a cheap drug that reduces bleeding in other conditions. A large trial of accident victims (other than those with head injury) found that it reduced the chances of bleeding to death. We wanted to find out if tranexamic acid would also reduce deaths among patients with head injuries. We studied just under 13,000 patients with traumatic brain injury who did not have other major injuries to their bodies from 175 hospitals across 29 countries. Patients were assigned at random to receive either tranexamic acid or a dummy medicine called a placebo. Neither the clinical team nor the patient knew which medicine the patient received. All patients received the usual treatments given to head-injured patients. Outcomes from 9127 participants were analysed. Among patients treated early, within 3 hours, the rate of head injury death was 18.5% (855/4613) in the tranexamic acid group and 19.8% (892/4514) in the placebo group. We found no evidence of an effect of tranexamic acid overall. However, in patients with mild or moderate traumatic brain injury, there was a 20% reduction in deaths. There were no side effects and no increase in disability in survivors when the drug was used. The economic analysis shows that tranexamic acid represents value for money for patients with mild or moderate traumatic brain injury.

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.

Global health, global surgery and mass casualties: II. Mass casualty centre resources, equipment and implementation.

Trauma/stroke centres optimise acute 24/7/365 surgical/critical care in high-income countries (HICs). Concepts from low-income and middle-income countries (LMICs) offer additional cost-effective healthcare strategies for limited-resource settings when combined with the trauma/stroke centre concept. Mass casualty centres (MCCs) integrate resources for both routine and emergency care-from prevention to acute care to rehabilitation. Integration of the various healthcare systems-governmental, non-governmental and military-is key to avoid both duplication and gaps. With input from LMIC and HIC personnel of various backgrounds-trauma and subspecialty surgery, nursing, information technology and telemedicine, and healthcare administration-creative solutions to the challenges of expanding care (both daily and disaster) are developed. MCCs are evolving initially in Chile and Pakistan. Technologies for cost-effective healthcare in LMICs include smartphone apps (enhance prehospital care) to electronic data collection and analysis (quality improvement) to telemedicine and drones/robots (support of remote regions and resource optimisation during both daily care and disasters) to resilient, mobile medical/surgical facilities (eg, battery-operated CT scanners). The co-ordination of personnel (within LMICs, and between LMICs and HICs) and the integration of cost-effective advanced technology are features of MCCs. Providing quality, cost-effective care 24/7/365 to the 5 billion who lack it presently makes MCCs an appealing means to achieve the healthcare-related United Nations Sustainable Development Goals for 2030.

Early tranexamic acid in traumatic brain injury: Evidence for an effective therapy.

The guidelines for management of traumatic brain injury (TBI) are based largely on measures to maintain an optimum internal milieu for prevention of secondary brain injury and enhancing recovery. One of the most common reasons for worsening outcomes following TBI is expanding intracranial haematoma which is compounded by the fibrinolytic physiology that follows TBI. Tranexamic acid (TXA) has a time tested role in preventing poor outcomes linked to excessive haemorrhage in trauma patients. Historically, patients with isolated head trauma were excluded from TXA use due to a theoretical increased risk of thrombosis. Recent evidence that redefines the beneficial role of early TXA administration in preventing mortality amongst patients with TBI is now at hand and offers a real prospect of a pharmacological intervention that would be adopted as a recommendation based on Class l evidence.

Hemorrhagic complications after decompressive craniectomy.

BACKGROUND: Decompressive craniectomy (DC) is the preferred surgical management option for lowering refractory intracranial pressure in cases of traumatic brain injury (TBI). A number of randomized controlled trials have demonstrated decreased mortality but increased morbidity following DC for TBI patients. Here, we reviewed the frequency of postoperative hemorrhagic complications following DC correlating with poor outcomes. METHODS: We retrospectively reviewed the medical records of patients who presented with TBI and underwent DC during the years 2015-2017. The frequency and characteristics of hemorrhagic complications were correlated with the patients' outcomes. RESULTS: There were 74 patients with TBI included in the study who underwent DC. Of these, 31 patients developed expansion of existing hemorrhagic lesions, 13 had new contusions, three developed new extradural hemorrhages, two developed new subdural hematomas, and one patient developed an intraventricular hemorrhage. Those who developed expansion of existing hemorrhagic lesions following DC had longer ICU stays and poorer outcomes (Glasgow outcome scale). CONCLUSION: After 74 DC performed in TBI patients, 67% developed new hemorrhagic lesions or expansion of previously existing hemorrhages. This finding negatively impacted clinical outcomes, including mortality.

Emergency care surveillance and emergency care registries in low-income and middle-income countries: conceptual challenges and future directions for research.

Despite the fact that the 15 leading causes of global deaths and disability-adjusted life years are from conditions amenable to emergency care, and that this burden is highest in low-income and middle-income countries (LMICs), there is a paucity of research on LMIC emergency care to guide policy making, resource allocation and service provision. A literature review of the 550 articles on LMIC emergency care published in the 10-year period from 2007 to 2016 yielded 106 articles for LMIC emergency care surveillance and registry research. Few articles were from established longitudinal surveillance or registries and primarily composed of short-term data collection. Using these articles, a working group was convened by the US National Institutes of Health Fogarty International Center to discuss challenges and potential solutions for established systems to better understand global emergency care in LMICs. The working group focused on potential uses for emergency care surveillance and registry data to improve the quality of services provided to patients. Challenges included a lack of dedicated resources for such research in LMIC settings as well as over-reliance on facility-based data collection without known correlation to the overall burden of emergency conditions in the broader community. The group outlined potential solutions including incorporating data from sources beyond traditional health records, use of standard clinical forms that embed data needed for research and policy making and structured population-based research to establish clear linkages between what is seen in emergency units and the wider community. The group then identified current gaps in LMIC emergency care surveillance and registry research to form a research agenda for the future.

Diffuse Low-Grade Glioma - Changing Concepts in Diagnosis and Management: A Review.

Though diffuse low-grade gliomas (dLGGs) represent only 15% of gliomas, they have been receiving increasing attention in the past decade. Significant advances in knowledge of the natural history and clinical diversity have been documented, and an improved pathological classification of gliomas that integrates histological features with molecular markers has been issued by the WHO. Advances in the radiological assessment of dLGG, particularly new magnetic resonance imaging scanning sequences, allow improved diagnostic and prognostic information. The management paradigms are evolving from "wait and watch" of the past to more active interventional therapy to obviate the risk of malignant transformation. New surgical technologies allow more aggressive surgical resections with a reduction of morbidity. Many reports suggest the association of gross total resection with longer overall survival and progression-free survival in addition to better seizure control. The literature also shows the use of chemotherapeutics and radiation therapy as important adjuncts to surgery. The goals of management have has been increasing survival with increasing stress on quality of life. Our review highlights the recent advances in the molecular diagnosis and management of dLGG with trends toward multidisciplinary and multimodality management of dLGG with an aim to surgically resect the primary disease, followed by chemoradiation in cases of progressive or recurrent disease.

Primary Trauma Care: A Training Course for Healthcare Providers in Developing Countries.

Outcomes of injury in low and middle income countries may be compromised by skill deficiencies of healthcare providers. Short subspecialty training courses can be a useful solution to skill-deficits. We report on the Primary Trauma Care programme, a 2-day course designed to train frontline health workers in resuscitation and early management of the injured with limited resources and equipment. Developed for use in weak health systems and now conducted in over 70 countries, the programme is cost-efficient with built-in design sustainability by way of early transfer of ownership to local partners to effect a cascade of trauma courses in their communities. Published studies report a significant improvement in both knowledge and skills of the participants with greater confidence in managing trauma victims. A trained health workforce could address the unmet needs identified by Global Surgery and thus contribute to achieving the Sustainable Development Goals.

Global health, global surgery and mass casualties. I. Rationale for integrated mass casualty centres.

It has been well-documented recently that 5 billion people globally lack surgical care. Also well-documented is the need to improve mass casualty disaster response. Many of the United Nations (UN) Sustainable Development Goals (SDGs) for 2030-healthcare and economic milestones-require significant improvement in global surgical care, particularly in low-income and middle-income countries. Trauma/stroke centres evolved in high-income countries with evidence that 24/7/365 surgical and critical care markedly improved morbidity and mortality for trauma and stroke and for cardiovascular events, difficult childbirth, acute abdomen. Duplication of emergency services, especially civilian and military, often results in suboptimal, expensive care. By combining all healthcare resources within the ongoing healthcare system, more efficient care for both individual emergencies and mass casualty situations can be achieved. We describe progress in establishing mass casualty centres in Chile and Pakistan. In both locations, planning among the stakeholders (primarily civilian and military) indicates the feasibility of such integrated surgical and emergency care. We also review other programmes and initiatives to provide integrated mass casualty disaster response. Integrated mass casualty centres are a feasible means to improve both day-to-day surgical care and mass casualty disaster response. The humanitarian aspect of mass casualty disasters facilitates integration among stakeholders-from local healthcare systems to military resources to international healthcare organisations. The benefits of mass casualty centres-both healthcare and economic-can facilitate achieving the 2030 UN SDGs.

Tranexamic acid for significant traumatic brain injury (The CRASH-3 trial): Statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial.

Background: Worldwide, traumatic brain injury (TBI) kills or hospitalises over 10 million people each year. Early intracranial bleeding is common after TBI, increasing the risk of death and disability. Tranexamic acid reduces blood loss in surgery and death due to bleeding in trauma patients with extra-cranial injury. Early administration of tranexamic acid in TBI patients might limit intracranial bleeding, reducing death and disability. The CRASH-3 trial aims to provide evidence on the effect of tranexamic acid on death and disability in TBI patients. We will randomly allocate about 13,000 TBI patients (approximately 10,000 within 3 hours of injury) to an intravenous infusion of tranexamic acid or matching placebo in addition to usual care. This paper presents a protocol update (version 2.1) and statistical analysis plan for the CRASH-3 trial. Results: The primary outcome is head injury death in hospital within 28 days of injury for patients treated within 3 hours of injury (deaths in patients treated after 3 hours will also be reported). Because there are reasons to expect that tranexamic acid will be most effective in patients treated immediately after injury and less effective with increasing delay, the effect in patients treated within one hour of injury is of particular interest. Secondary outcomes are all-cause and cause-specific mortality, vascular occlusive events, disability based on the Disability Rating Scale and measures suggested by patient representatives, seizures, neurosurgical intervention, neurosurgical blood loss, days in intensive care and adverse events. Sub-group analyses will examine the effect of tranexamic acid on head injury death stratified by time to treatment, severity of TBI and baseline risk. Conclusion: The CRASH-3 trial will provide reliable evidence of the effectiveness and safety of tranexamic acid in patients with acute TBI. Registration: International Standard Randomised Controlled Trials registry ( ISRCTN15088122) 19/07/2011, and ClinicalTrials.gov ( NCT01402882) 25/07/2011.

Descriptive epidemiology of Karachi road traffic crash mortality in 2015.

The Karachi city's Road Traffic Injury Research and Prevention Center (RTIRPC), collects Road Traffic Crash (RTC) data on injuries and fatalities from three major public and private hospitals' emergency departments. In the year 2015, 1021 deaths were recorded; with 871 (85.3%) deaths in males. Cumulatively, 286 (28.0%) deaths were recorded in the 21-30year age group, and for 198 (19.4%) RTC fatal victims, the primary vehicle involved was motorbike. Highest number of fatalities were recorded in the month of January i.e. 153 (15.0%), while the lowest number was recorded for June, with 47 (4.6%) fatalities. RTIRPC is a unique surveillance system in Pakistan providing RTC morbidity and mortality burden and trends in the city that needs to be expanded in Karachi, and extended throughout the country to better choreograph preventive measures including health promotion campaigns.