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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.)

Objectives: We investigated whether comorbidity burden of comatose survivors of out-of-hospital cardiac arrest (OHCA) affects outcome and if comorbidity modifies the effect of target temperature management (TTM) on final outcome., Design: The TTM trial randomized 939 patients to 24 h of TTM at either 33 or 36 °C with no difference regarding mortality and neurological outcome. This post-hoc study of the TTM-trial formed a modified comorbidity index (mCI), based on available comorbidities from the Charlson comorbidity index (CCI)., Results: Bystander cardiopulmonary resuscitation (CPR) decreased with higher comorbidity group, p = 0.01. Comorbidity groups were univariately associated with higher mortality compared to mCI0 (HR mCI1 : 1.55, CI: 1.25-1.93, p < 0.001, HR mCI2 : 2.01, CI: 1.55-2.62, p < 0.001, HR mCI ≥ 3 : 2.16, CI: 1.57-2.97, p < 0.001). When adjusting for confounders there was a consistent, nonsignificant association between level of comorbidity and mortality (HRm C11 : 1.17, CI: 0.92-1.48, p = 0.21, HR mCI2 : 1.28, CI: 0.96-1.71, p = 0.10, HR mCI ≥ 3 : 1.37, CI: 0.97-1.95, p = 0.08). There was no interaction between comorbidity burden and level of TTM on outcome, p = 0.61., Conclusion: Comorbidity burden was associated with higher mortality following OHCA, but when adjusting for confounders, the influence was no longer significant. The association between mCI and mortality was not modified by TTM. Comorbidity burden is associated with lower rates of bystander cardiopulmonary resuscitation after OHCA.

Aim: Time to Return of Spontaneous Circulation (ROSC) has a plausible relation to severity of hypoxic injury before and during resuscitation in Out-of-Hospital Cardiac Arrest (OHCA), and has consistently been associated with adverse outcome. The effect of Targeted Temperature Management (TTM) may not be similar over the full spectrum of time to ROSC. This study investigated the possible beneficial effect of targeting 33°C over 36°C on the prognostic importance of time to ROSC., Methods: In predefined sub-study of the TTM-trial (NEJM 2013) we investigated the relationship between time to ROSC, level of TTM and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) scale and modified Rankin Scale (mRS) after 180 days., Results: Prolonged time to ROSC was significantly associated with increased mortality with a hazard ratio (HR) of 1.02 per minute (95% CI 1.01-1.02). Level of TTM did not modify the association of time to ROSC and mortality, pinteraction=0.85. Prolonged time to ROSC was associated with reduced odds of surviving with a favorable neurological outcome for CPC (p=0.008 for CPC 1-2) and mRS (p=0.17, mRS 0-3) with no significant interaction with level of TTM., Conclusion: Time to ROSC remains a significant prognostic factor in comatose OHCA patients with regards to risk of death and risk of adverse neurological outcome. For any time to ROSC, targeting 33°C in TTM was not associated with benefit with regards to reducing mortality or risk of adverse neurological outcome compared to targeting 36°C., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aim: Comparing the outcome after out-of-hospital cardiac arrest (OHCA) in men and women and to determine whether sex modifies the effect of targeted temperature management (TTM) at 33 or 36°C., Methods: The TTM trial randomized 950 patients to TTM at 33 or 36°C for 24h. This predefined sub-study of the TTM trial assessed survival and neurological outcome defined as Cerebral Performance Category (CPC) and modified Rankin Scale (mRS) using female sex as main predictor of outcome, in relation to level of TTM and other confounding factors., Results: Compared to men, women more often had OHCA at home, p=0.04 and less often had bystander defibrillation, p=0.01. No other differences in arrest circumstances were found. Coronary angiography (CAG) and percutaneous coronary intervention (PCI) <24h after ROSC was less often performed in women, both: p=0.02. Female sex was associated with higher mortality in univariate analysis, hazard ratio (HR)=1.29, CI=1.04-1.61, p=0.02 compared to men. Adjusting for demographic factors (age and comorbidity), arrest circumstances, pre-hospital findings, inclusion sites, treatments and status at admission reduced this: HR=1.11, CI=0. 87-1.41, p=0.42, and sex was no longer an independent risk factor for death. The effect of sex did not modify the effect of TTM at 33 and 36°C, pinteraction=0.73., Conclusion: Female sex seems associated with adverse outcome, but this association is largely explained by differences in arrest circumstances and in-hospital treatment. Our data shows no interaction between sex and the effect of targeting 33 vs. 36°C., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Neuron-specific enolase (NSE) is a widely-used biomarker for prognostication of neurological outcome after cardiac arrest, but the relevance of recommended cutoff values has been questioned due to the lack of a standardized methodology and uncertainties over the influence of temperature management., Objectives: This study investigated the role of NSE as a prognostic marker of outcome after out-of-hospital cardiac arrest (OHCA) in a contemporary setting., Methods: A total of 686 patients hospitalized after OHCA were randomized to targeted temperature management at either 33°C or 36°C. NSE levels were assessed in blood samples obtained 24, 48, and 72 h after return of spontaneous circulation. The primary outcome was neurological outcome at 6 months using the cerebral performance category score., Results: NSE was a robust predictor of neurological outcome in a baseline variable-adjusted model, and target temperature did not significantly affect NSE values. Median NSE values were 18 ng/ml versus 35 ng/ml, 15 ng/ml versus 61 ng/ml, and 12 ng/ml versus 54 ng/ml for good versus poor outcome at 24, 48, and 72 h, respectively (p < 0.001). At 48 and 72 h, NSE predicted neurological outcome with areas under the receiver-operating curve of 0.85 and 0.86, respectively. High NSE cutoff values with false positive rates ≤5% and tight 95% confidence intervals were able to reliably predict outcome., Conclusions: High, serial NSE values are strong predictors of poor outcome after OHCA. Targeted temperature management at 33°C or 36°C does not significantly affect NSE levels. (Target Temperature Management After Cardiac Arrest [TTM]; NCT01020916)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.)