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Background: Critically ill patients in the intensive care unit (ICU) are at risk of clinically important gastrointestinal bleeding, and acid suppressants are frequently used prophylactically. However, stress ulcer prophylaxis may increase the risk of serious adverse events and, additionally, the quantity and quality of evidence supporting the use of stress ulcer prophylaxis is low. The aim of the SUP-ICU trial is to assess the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the ICU. We hypothesise that stress ulcer prophylaxis reduces the rate of gastrointestinal bleeding, but increases rates of nosocomial infections and myocardial ischaemia. The overall effect on mortality is unpredictable.Methods/design: The SUP-ICU trial is an investigator-initiated, pragmatic, international, multicentre, randomised, blinded, parallel-group trial of stress ulcer prophylaxis with a proton pump inhibitor versus placebo (saline) in 3350 acutely ill ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90-day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischaemia, days alive without life support in the 90-day period, serious adverse reactions, 1-year mortality, and health economic analyses. The sample size will enable us to detect a 20 % relative risk difference (5 % absolute risk difference) in 90-day mortality assuming a 25 % event rate with a risk of type I error of 5 % and power of 90 %. The trial will be externally monitored according to Good Clinical Practice standards. Interim analyses will be performed after 1650 and 2500 patients.Conclusion: The SUP-ICU trial will provide high-quality data on the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in critically ill adult patients admitted in the ICU.Trial Registration: ClinicalTrials.gov Identifier: NCT02467621 . [ABSTRACT FROM AUTHOR]

Background: Animal experimental studies and previous randomized trials suggest an improvement in mortality and neurological function with temperature regulation to hypothermia after cardiac arrest. According to a systematic review, previous trials were small, had a risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management (TTM) strategy is not known. To prevent outcome reporting bias, selective reporting and data-driven results, we present the a priori defined detailed statistical analysis plan as an update to the previously published outline of the design and rationale for the TTM trial.Methods: The TTM trial is an investigator-initiated, multicenter, international, randomized, parallel-group, and assessor-blinded clinical trial of temperature management in 950 adult unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients are randomized to a TTM of either 33°C or 36°C after return of spontaneous circulation. The primary outcome is all-cause mortality at maximal follow-up (until end of the trial and a minimum of 180 days). The main secondary outcomes are the composite outcome of all-cause mortality and poor neurological function (Cerebral Performance Category (CPC) 3 and 4, and modified Rankin Scale (mRS) 4 and 5) at hospital discharge and at 180 days; and assessment of safety and harm: bleeding, infections, electrolyte and metabolic disorders, seizures, cardiac arrhythmia, and renal replacement therapy.Conclusion: The TTM trial investigates potential benefit and harm of two target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.Trial Registration: ClinicalTrials.gov identifier: NCT01020916. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to describe out-of-hospital cardiac arrest (OHCA) survivors' ability to participate in activities of everyday life and society, including return to work. The specific aim was to evaluate potential effects of cognitive impairment., Methods and Results: Two hundred eighty-seven OHCA survivors included in the TTM trial (Target Temperature Management) and 119 matched control patients with ST-segment-elevation myocardial infarction participated in a follow-up 180 days post-event that included assessments of participation, return to work, emotional problems, and cognitive impairment. On the Mayo-Portland Adaptability Inventory-4 Participation Index, OHCA survivors (n=270) reported more restricted participation In everyday life and in society (47% versus 30%; P <0.001) compared with ST-segment-elevation myocardial infarction controls (n=118). Furthermore, 27% (n=36) of pre-event working OHCA survivors (n=135) compared with 7% (n=3) of pre-event working ST-segment-elevation myocardial infarction controls (n=45) were on sick leave (odds ratio, 4.9; 95% confidence interval, 1.4-16.8; P =0.01). Among the OHCA survivors assumed to return to work (n=135), those with cognitive impairment (n=55) were 3× more likely (odds ratio, 3.3; 95% confidence interval, 1.2-9.3; P =0.02) to be on sick leave compared with those without cognitive impairment (n=40; 36%, n=20, versus 15%, n=6). For OHCA survivors, the variables that were found most predictive for a lower participation were depression, restricted mobility, memory impairment, novel problem-solving difficulties, fatigue, and slower processing speed., Conclusions: OHCA survivors reported a more restricted societal participation 6 months post-arrest, and their return to work was lower compared with ST-segment-elevation myocardial infarction controls. Cognitive impairment was significantly associated with lower participation, together with the closely related symptoms of fatigue, depression, and restricted mobility. These predictive variables may be used during follow-up to identify OHCA survivors at risk of a less successful recovery that may benefit from further support and rehabilitation., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01946932., (© 2018 American Heart Association, Inc.)

Background: Target temperature management is recommended as a neuroprotective strategy after out-of-hospital cardiac arrest. Potential effects of different target temperatures on cognitive impairment commonly described in survivors have not been investigated sufficiently. The primary aim of this study was to evaluate whether a target temperature of 33°C compared with 36°C was favorable for cognitive function; the secondary aim was to describe cognitive impairment in cardiac arrest survivors in general., Methods and Results: Study sites included 652 cardiac arrest survivors originally randomized and stratified for site to temperature control at 33°C or 36°C within the Target Temperature Management trial. Survival until 180 days after the arrest was 52% (33°C, n=178/328; 36°C, n=164/324). Survivors were invited to a face-to-face follow-up, and 287 cardiac arrest survivors (33°C, n=148/36°C, n=139) were assessed with tests for memory (Rivermead Behavioural Memory Test), executive functions (Frontal Assessment Battery), and attention/mental speed (Symbol Digit Modalities Test). A control group of 119 matched patients hospitalized for acute ST-segment-elevation myocardial infarction without cardiac arrest performed the same assessments. Half of the cardiac arrest survivors had cognitive impairment, which was mostly mild. Cognitive outcome did not differ (P>0.30) between the 2 temperature groups (33°C/36°C). Compared with control subjects with ST-segment-elevation myocardial infarction, attention/mental speed was more affected among cardiac arrest patients, but results for memory and executive functioning were similar., Conclusions: Cognitive function was comparable in survivors of out-of-hospital cardiac arrest when a temperature of 33°C and 36°C was targeted. Cognitive impairment detected in cardiac arrest survivors was also common in matched control subjects with ST-segment-elevation myocardial infarction not having had a cardiac arrest., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01946932., (© 2015 American Heart Association, Inc.)