Among patients receiving aspirin and clopidogrel, prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding. There was no apparent cardiovascular interaction between clopidogrel and omeprazole, but our results do not rule out a clinically meaningful difference in cardiovascular events due to use of a PPI. (Funded by Cogentus Pharmaceuticals; ClinicalTrials.gov number, NCT00557921.).

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.

Secondary ischemic insults caused by systemic factors after severe head injury can be prevented with a targeted management protocol. However, potential adverse effects of this management strategy may offset these beneficial effects.

clinicaltrials.gov Identifier: NCT01235351.

sis are at elevated risk of ischemic events but, depending on their specific manifestations of atherothrombosis, may have varying degrees of future risk for ischemic events. Accurate knowledge of the major determinants of subsequent ischemic risk would be extremely useful, both for clinical and investigational purposes. Several recent clinical trials of new agentsinacutecoronarysyndromes,stable atherosclerosis,anddiabetesmellitushave reported event rates lower than initially projected. 1-6 Theabilitytoidentifypatients at highest risk of cardiovascular events would allow trials of novel therapies to focus on those patients most likely to derive benefit. For clinicians, the ability to identify rapidly the major determinants of risk among patients with atherosclerosis would be useful to triage novel preventive therapies toward those at the higher end of the risk spectrum. Thus, the international Reduction of Atherothrom-bosisforContinuedHealth(REACH)Registry, a contemporary data set comprising patients with various manifestations of atherosclerosis, spanning from asymptomaticadultswithriskfactors,topatients with stable atherosclerosis, to those with prior ischemic events, would be potentially useful to establish the risk of future ischemicevents.Herein,the4-yearresults of the REACH Registry are presented.

Although this clinical trial was not designed to study the association of management strategy and the occurrence of ARDS, the data strongly indicated that induced hypertension in this high-risk group of patients is associated with the development of symptomatic ARDS.

Analysis of the PbtO2 monitoring data suggested that the likelihood of death increased with increasing duration of time at or below a PbtO2 of 15 torr (2.0 kPa) or with the occurrence of any PbtO2 values of < or =6 torr (< or =0.8 kPa).

The traditional practice of elevating the head in order to lower intracranial pressure (ICP) in head-injured patients has been challenged in recent years. Some investigators argue that patients with intracranial hypertension should be placed in a horizontal position, the rationale being that this will increase the cerebral perfusion pressure (CPP) and thereby improve cerebral blood flow (CBF). However, ICP is generally significantly higher when the patient is in the horizontal position. This study was undertaken to clarify the issue of optimal head position in the care of head-injured patients. The effect of 0 degree and 30 degrees head elevation on ICP, CPP, CBF, mean carotid pressure, and other cerebral and systemic physiological parameters was studied in 22 head-injured patients. The mean carotid pressure was significantly lower when the patient's head was elevated at 30 degrees than at 0 degrees (84.3 +/- 14.5 mm Hg vs. 89.5 +/- 14.6 mm Hg), as was the mean ICP (14.1 +/- 6.7 mm Hg vs. 19.7 +/- 8.3 mm Hg). There was no statistically significant change in CPP, CBF, cerebral metabolic rate of oxygen, arteriovenous difference of lactate, or cerebrovascular resistance associated with the change in head position. The data indicate that head elevation to 30 degrees significantly reduced ICP in the majority of the 22 patients without reducing CPP or CBF.