A concerted effort to tackle the global health problem posed by traumatic brain injury (TBI) is long overdue. TBI is a public health challenge of vast, but insufficiently recognised, proportions. Worldwide, more than 50 million people have a TBI each year, and it is estimated that about half the world's population will have one or more TBIs over their lifetime. TBI is the leading cause of mortality in young adults and a major cause of death and disability across all ages in all countries, with a disproportionate burden of disability and death occurring in low-income and middle-income countries (LMICs). It has been estimated that TBI costs the global economy approximately $US400 billion annually. Deficiencies in prevention, care, and research urgently need to be addressed to reduce the huge burden and societal costs of TBI. This Commission highlights priorities and provides expert recommendations for all stakeholders—policy makers, funders, health-care professionals, researchers, and patient representatives—on clinical and research strategies to reduce this growing public health problem and improve the lives of people with TBI.Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Söderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbüchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigator

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Background-Neurohormones are considered markers of heart failure progression. We examined whether changes in brain natriuretic peptide (BNP) and norepinephrine (NE) over time are associated with corresponding changes in mortality and morbidity in the Valsartan Heart Failure Trial. Methods and Results-Plasma BNP and NE were measured before randomization and during follow-up in Ϸ4300 patients in the Valsartan Heart Failure Trial. The relation between baseline BNP and NE and all-cause mortality and first morbid event (M&M) was analyzed in subgroups, with values above and below the median, and by quartiles. The change and percent change from baseline to 4 and 12 months in BNP and NE were also analyzed by quartiles for subsequent M&M. Risk ratios for M&M were calculated using a Cox proportional hazard model. Risk ratio of M&M for patients with baseline BNP or NE above the median was significantly higher than that for patients with values below the median. Baseline BNP and NE in quartiles also showed a quartile-dependent increase in M&M. BNP had a stronger association with M&M than NE. Patients with the greatest percent decrease in BNP and NE from baseline to 4 and 12 months had the lowest whereas patients with greatest percent increase in BNP and NE had the highest M&M. Conclusions-Not only are plasma BNP and NE important predictors of heart failure M&M, but changes in these neurohormones over time are associated with corresponding changes in M&M. These data further reinforce their role as significant surrogate markers in HF and underscore the importance of including their measurement in HF trials.

Background-Circulating cardiac troponin T, a marker of cardiomyocyte injury, predicts adverse outcome in patients with heart failure (HF) but is detectable in only a small fraction of those with chronic stable HF. We assessed the prognostic value of circulating cardiac troponin T in patients with stable chronic HF with a traditional (cTnT) and a new precommercial highly sensitive assay (hsTnT). Methods and Results-Plasma troponin T was measured in 4053 patients with chronic HF enrolled in the Valsartan HeartFailure Trial (Val-HeFT). Troponin T was detectable in 10.4% of the population with the cTnT assay (detection limit Յ0.01 ng/mL) compared with 92.0% with the new hsTnT assay (Յ0.001 ng/mL). Patients with cTnT elevation or with hsTnT above the median (0.012 ng/mL) had more severe HF and worse outcome. In Cox proportional hazards models adjusting for clinical risk factors, cTnT was associated with death (780 events; hazard ratioϭ2. Key Words: heart failure Ⅲ natriuretic peptides Ⅲ prognosis Ⅲ troponin C ardiac troponins I and T (cTnT) are sensitive and specific markers of myocardial injury used routinely for the diagnosis of acute coronary syndromes. 1-5 Elevated troponin blood levels have been reported in several cohorts of patients with heart failure (HF), and the magnitude of elevation has been correlated with the severity of the disease and with adverse outcomes. 6 -16 Because of their high cardiac specificity, elevated troponins in patients with HF may suggest ongoing myocardial damage and may serve as a marker for the progression of HF. Measurement of troponin has been proposed since 1997 to monitor patients with HF. 17,18 The prevalence of elevated troponin T in the general population is Ͻ1% and is associated with underlying cardiovascular disease or high-risk phenotypes. 19 Editorial p 1217 Clinical Perspective p 1249The levels of cardiac troponins in HF are generally lower than those in patients with acute coronary syndromes and lack the characteristic rise and fall pattern. 4 Few reports exist on cTnT elevations in chronic stable HF. 6,8,16,20 Previous studies included more frequently patients with severe HF (New York Heart Association [NYHA] class III and IV) and/or with decompensated HF, recruited in a single center. 6,8,10,11,15,16 As expected, lesser severity of HF is associated with a larger fraction of patients with undetectable troponin. The commercial assays for troponins have sufficient sensitivity (0.01 ng/mL) for screening patients with suspected myocardial infarction 21 but may be inadequate for risk stratification of patients with stable chronic HF who may have levels below Methods Study Design and PatientsVal-HeFT was a randomized, placebo-controlled, double-blind, parallel-arm multicenter trial of 5010 patients with stable, symptomatic HF, who were on prescribed HF therapy. The patients had a left ventricular ejection fraction (LVEF) Ͻ40% and a left ventricular diameter in diastole adjusted for body surface area (LVIDD/BSA) Ն2.9 cm/m 2 . Results of the main trial have been published....