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/

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

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

Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

BACKGROUND: Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. FINDINGS: Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9-3·0) for men and 3·5 years (3·4-3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78-0·92) and 1·2 years (1·1-1·3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. INTERPRETATION: Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum. FUNDING: Bill & Melinda Gates Foundation

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

Nations within a nation: variations in epidemiological transition across the states of India, 1990-2016 in the Global Burden of Disease Study.

BACKGROUND: 18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016. METHODS: Using all available data sources, the India State-Level Disease Burden Initiative estimated burden (metrics were deaths, disability-adjusted life-years [DALYs], prevalence, incidence, and life expectancy) from 333 disease conditions and injuries and 84 risk factors for each state of India from 1990 to 2016 as part of GBD 2016. We divided the states of India into four epidemiological transition level (ETL) groups on the basis of the ratio of DALYs from communicable, maternal, neonatal, and nutritional diseases (CMNNDs) to those from non-communicable diseases (NCDs) and injuries combined in 2016. We assessed variations in the burden of diseases and risk factors between ETL state groups and between states to inform a more specific health-system response in the states and for India as a whole. FINDINGS: DALYs due to NCDs and injuries exceeded those due to CMNNDs in 2003 for India, but this transition had a range of 24 years for the four ETL state groups. The age-standardised DALY rate dropped by 36·2% in India from 1990 to 2016. The numbers of DALYs and DALY rates dropped substantially for most CMNNDs between 1990 and 2016 across all ETL groups, but rates of reduction for CMNNDs were slowest in the low ETL state group. By contrast, numbers of DALYs increased substantially for NCDs in all ETL state groups, and increased significantly for injuries in all ETL state groups except the highest. The all-age prevalence of most leading NCDs increased substantially in India from 1990 to 2016, and a modest decrease was recorded in the age-standardised NCD DALY rates. The major risk factors for NCDs, including high systolic blood pressure, high fasting plasma glucose, high total cholesterol, and high body-mass index, increased from 1990 to 2016, with generally higher levels in higher ETL states; ambient air pollution also increased and was highest in the low ETL group. The incidence rate of the leading causes of injuries also increased from 1990 to 2016. The five leading individual causes of DALYs in India in 2016 were ischaemic heart disease, chronic obstructive pulmonary disease, diarrhoeal diseases, lower respiratory infections, and cerebrovascular disease; and the five leading risk factors for DALYs in 2016 were child and maternal malnutrition, air pollution, dietary risks, high systolic blood pressure, and high fasting plasma glucose. Behind these broad trends many variations existed between the ETL state groups and between states within the ETL groups. Of the ten leading causes of disease burden in India in 2016, five causes had at least a five-times difference between the highest and lowest state-specific DALY rates for individual causes. INTERPRETATION: Per capita disease burden measured as DALY rate has dropped by about a third in India over the past 26 years. However, the magnitude and causes of disease burden and the risk factors vary greatly between the states. The change to dominance of NCDs and injuries over CMNNDs occurred about a quarter century apart in the four ETL state groups. Nevertheless, the burden of some of the leading CMNNDs continues to be very high, especially in the lowest ETL states. This comprehensive mapping of inequalities in disease burden and its causes across the states of India can be a crucial input for more specific health planning for each state as is envisioned by the Government of India's premier think tank, the National Institution for Transforming India, and the National Health Policy 2017. FUNDING: Bill & Melinda Gates Foundation; Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India; and World Bank

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