Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study).

OBJECTIVE: To assess the effect of tranexamic acid (which reduces bleeding in surgical patients and reduces mortality due to bleeding in trauma patients) on intracranial haemorrhage in patients with traumatic brain injury. METHODS: A nested, randomised, placebo controlled trial. All investigators were masked to treatment allocation. All analyses were by intention to treat. Patients 270 adult trauma patients with, or at risk of, significant extracranial bleeding within 8 hours of injury, who also had traumatic brain injury. INTERVENTIONS: Patients randomly allocated to tranexamic acid (loading dose 1 g over 10 minutes, then infusion of 1 g over 8 hours) or matching placebo. MAIN OUTCOME MEASURES: Intracranial haemorrhage growth (measured by computed tomography) between hospital admission and then 24-48 hours later, with adjustment for Glasgow coma score, age, time from injury to the scans, and initial haemorrhage volume. RESULTS: Of the 133 patients allocated to tranexamic acid and 137 allocated to placebo, 123 (92%) and 126 (92%) respectively provided information on the primary outcome. All patients provided information on clinical outcomes. The mean total haemorrhage growth was 5.9 ml (SD 26.8) and 8.1 mL (SD 29.2) in the tranexamic acid and placebo groups respectively (adjusted difference -3.8 mL (95% confidence interval -11.5 to 3.9)). New focal cerebral ischaemic lesions occurred in 6 (5%) patients in the tranexamic acid group versus 12 (9%) in the placebo group (adjusted odds ratio 0.51 (95% confidence interval 0.18 to 1.44)). There were 14 (11%) deaths in the tranexamic acid group and 24 (18%) in the placebo group (adjusted odds ratio 0.47 (0.21 to 1.04)). CONCLUSIONS: This trial shows that neither moderate benefits nor moderate harmful effects of tranexamic acid in patients with traumatic brain injury can be excluded. However, the analysis provides grounds for further clinical trials evaluating the effect of tranexamic acid in this population. Trial registration ISRCTN86750102

CRASH - Corticosteroid Randomisation after Significant Head Injury

A large simple placebo controlled trial, among adults with head injury and impaired consciousness, of the effects of a 48-hour infusion of corticosteroids on death and neurological disability. CRASH was a randomised, controlled, double-blind trial undertaken in 239 hospitals in 49 countries. A total of 10008 adults with head injury and a Glasgow Coma Score (GCS) of 14 or less within 8 hours of injury were randomly allocated 48 hour infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation and analysis was by intention to treat. Access to this dataset is available via https://freebird.lshtm.ac.uk/

Stroke treatment academic industry roundtable recommendations for individual data pooling analyses in stroke

Pooled analysis of individual patient data from stroke trials can deliver more precise estimates of treatment effect, enhance power to examine prespecified subgroups, and facilitate exploration of treatment-modifying influences. Analysis plans should be declared, and preferably published, before trial results are known. For pooling trials that used diverse analytic approaches, an ordinal analysis is favored, with justification for considering deaths and severe disability jointly. Because trial pooling is an incremental process, analyses should follow a sequential approach, with statistical adjustment for iterations. Updated analyses should be published when revised conclusions have a clinical implication. However, caution is recommended in declaring pooled findings that may prejudice ongoing trials, unless clinical implications are compelling. All contributing trial teams should contribute to leadership, data verification, and authorship of pooled analyses. Development work is needed to enable reliable inferences to be drawn about individual drug or device effects that contribute to a pooled analysis, versus a class effect, if the treatment strategy combines ≥2 such drugs or devices. Despite the practical challenges, pooled analyses are powerful and essential tools in interpreting clinical trial findings and advancing clinical care

Magnetic Doppler Imaging of He-strong star HD 184927

We have employed an extensive new timeseries of Stokes I and V spectra obtained with the ESPaDOnS spectropolarimeter at the 3.6-m Canada-France-Hawaii Telescope to investigate the physical parameters, chemical abundance distributions and magnetic field topology of the slowly-rotating He-strong star HD 184927. We infer a rotation period of 9.53071+-0.00120 from H-alpha, H-beta, LSD magnetic measurements and EWs of helium lines. We used an extensive NLTE TLUSTY grid along with the SYNSPEC code to model the observed spectra and find a new value of luminosity. In this poster we present the derived physical parameters of the star and the results of Magnetic Doppler Imaging analysis of the Stokes I and V profiles. Wide wings of helium lines can be described only under the assumption of the presence of a large, very helium-rich spot

Distribution of selected healthcare resources for influenza pandemic response in Cambodia.

INTRODUCTION: Human influenza infection poses a serious public health threat in Cambodia, a country at risk for the emergence and spread of novel influenza viruses with pandemic potential. Prior pandemics demonstrated the adverse impact of influenza on poor communities in developing countries. Investigation of healthcare resource distribution can inform decisions regarding resource mobilization and investment for pandemic mitigation. METHODS: A health facility survey performed across Cambodia obtained data on availability of healthcare resources important for pandemic influenza response. Focusing on five key resources considered most necessary for treating severe influenza (inpatient beds, doctors, nurses, oseltamivir, and ventilators), resource distributions were analyzed at the Operational District (OD) and Province levels, refining data analysis from earlier studies. Resources were stratified by respondent type (hospital vs. District Health Office [DHO]). A summary index of distribution inequality was calculated using the Gini coefficient. Indices for local spatial autocorrelation were measured at the OD level using geographical information system (GIS) analysis. Finally, a potential link between socioeconomic status and resource distribution was explored by mapping resource densities against poverty rates. RESULTS: Gini coefficient calculation revealed variable inequality in distribution of the five key resources at the Province and OD levels. A greater percentage of the population resides in areas of relative under-supply (28.5%) than over-supply (21.3%). Areas with more resources per capita showed significant clustering in central Cambodia while areas with fewer resources clustered in the northern and western provinces. Hospital-based inpatient beds, doctors, and nurses were most heavily concentrated in areas of the country with the lowest poverty rates; however, beds and nurses in Non-Hospital Medical Facilities (NHMF) showed increasing concentrations at higher levels of poverty. CONCLUSIONS: There is considerable heterogeneity in healthcare resource distribution across Cambodia. Distribution mapping at the local level can inform policy decisions on where to stockpile resources in advance of and for reallocation in the event of a pandemic. These findings will be useful in determining future health resource investment, both for pandemic preparedness and for general health system strengthening, and provide a foundation for future analyses of equity in health services provision for pandemic mitigation planning in Cambodia

Value of risk scores in the decision to palliate patients withruptured abdominal aortic aneurysm

Background: The aim of this study was to develop a 48‐h mortality risk score, which included morphology data, for patients with ruptured abdominal aortic aneurysm presenting to an emergency department, and to assess its predictive accuracy and clinical effectiveness in triaging patients to immediate aneurysm repair, transfer or palliative care. Methods: Data from patients in the IMPROVE (Immediate Management of the Patient With Ruptured Aneurysm: Open Versus Endovascular Repair) randomized trial were used to develop the risk score. Variables considered included age, sex, haemodynamic markers and aortic morphology. Backwards selection was used to identify relevant predictors. Predictive performance was assessed using calibration plots and the C‐statistic. Validation of the newly developed and other previously published scores was conducted in four external populations. The net benefit of treating patients based on a risk threshold compared with treating none was quantified. Results: Data from 536 patients in the IMPROVE trial were included. The final variables retained were age, sex, haemoglobin level, serum creatinine level, systolic BP, aortic neck length and angle, and acute myocardial ischaemia. The discrimination of the score for 48‐h mortality in the IMPROVE data was reasonable (C‐statistic 0·710, 95 per cent c.i. 0·659 to 0·760), but varied in external populations (from 0·652 to 0·761). The new score outperformed other published risk scores in some, but not all, populations. An 8 (95 per cent c.i. 5 to 11) per cent improvement in the C‐statistic was estimated compared with using age alone. Conclusion: The assessed risk scores did not have sufficient accuracy to enable potentially life‐saving decisions to be made regarding intervention. Focus should therefore shift to offering repair to more patients and reducing non‐intervention rates, while respecting the wishes of the patient and family

Vegetation response to the "African Humid Period" termination in Central Cameroon (7° N) – new pollen insight from Lake Mbalang

A new pollen sequence from the Lake Mbalang (7°19´ N, 13°44´ E, 1110 m a.s.l.) located on the eastern Adamawa plateau, in Central Cameroon, is presented in this paper to analyze the Holocene African Humid Period (AHP) termination and related vegetation changes at 7° N in tropical Africa, completing an important transect for exploring shifts in the northern margin of the African Monsoon. This sequence, spanning the last 7000 cal yr BP, shows that the vegetation response to this transitional climatic period was marked by significant successional changes within the broad context of long-term aridification. Semi-deciduous/sub-montane forest retreat in this area is initially registered as early as ca. 6100 cal yr BP and modern savannah was definitely established at ca. 3000 cal yr BP and stabilized at ca. 2400 cal yr BP; but a slight forest regeneration episode is observed between ca. 5200 and ca. 4200 cal yr BP. In this area with modern high rainfall, increasing in the length of the dry season during the AHP termination linked to a contraction of the northern margin of the Intertropical Convergence Zone (ITCZ) from ca. 6100 cal yr BP onward, probably associated with decreasing in cloud cover and/or fog frequency, has primarily controlled vegetation dynamics and above all the disappearance of the forested environment on the Adamawa plateau. Compared to previous studies undertaken in northern tropical and Central Africa, this work clearly shows that the response of vegetation to transitional periods between climatic extremes such as the AHP termination might be different in timing, mode and amplitude according to the regional climate of the study sites, but also according to the stability of vegetation before and during these climatic transitions