| 61. |
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| 62. |
- Dankiewicz, Josef, et al.
(författare)
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Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2): A randomized clinical trial - Rationale and design
- 2019
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 217, s. 23-31
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Tidskriftsartikel (refereegranskat)abstract
- Background: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore warranted. Methods: The TTM2-trial is an international, multicenter, parallel group, investigator-initiated, randomized, superiority trial in which a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and early treatment of fever (≥37.8°C). Participants will be randomized within 3 hours of return of spontaneous circulation with the intervention period lasting 40 hours in both groups. Sedation will be mandatory for all patients throughout the intervention period. The clinical team involved with direct patient care will not be blinded to allocation group due to the inherent difficulty in blinding the intervention. Prognosticators, outcome-assessors, the steering group, the trial coordinating team, and trial statistician will be blinded. The primary outcome will be all-cause mortality at 180 days after randomization. We estimate a 55% mortality in the control group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The main secondary neurological outcome will be poor functional outcome (modified Rankin Scale 4–6) at 180 days after arrest. Discussion: The TTM2-trial will compare hypothermia to 33°C with normothermia and early treatment of fever (≥37.8°C) after out-of-hospital cardiac arrest. © 2019
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| 63. |
- Dankiewicz, Josef, et al.
(författare)
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Time to start of cardiopulmonary resuscitation and the effect of target temperature management at 33°C and 36°C.
- 2016
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Ingår i: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 99, s. 44-49
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Tidskriftsartikel (refereegranskat)abstract
- The optimal temperature during targeted temperature management (TTM) for comatose patients resuscitated from out-of-hospital cardiac arrest is unknown. It has been hypothesized that patients with long no-flow times, for example those without bystander CPR would have the most to gain from temperature management at lower temperatures.
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| 64. |
- Devaux, Yvan, et al.
(författare)
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Association of circulating MicroRNA-124-3p levels with outcomes after out-of-hospital cardiac arrest : A substudy of a randomized clinical trial
- 2016
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Ingår i: JAMA Cardiology. - : American Medical Association (AMA). - 2380-6583. ; 1:3, s. 305-313
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The value of microRNAs (miRNAs) as biomarkers has been investigated in various clinical contexts. Initial small-scale studies suggested that miRNAs might be useful indicators of outcome after cardiac arrest. OBJECTIVE: To address the prognostic value of circulating miRNAs in a large cohort of comatose patients with out-of-hospital cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: This substudy of the Target Temperature Management After Cardiac Arrest (TTM) trial, a multicenter randomized, parallel-group, assessor-blinded clinical trial, compared the 6-month neurologic outcomes and survival of patients with cardiac arrest after targeted temperature management at 33°C or 36°C. Five hundred seventy-nine patients who survived the first 24 hours after the return of spontaneous circulation and who had blood samples available for miRNA assessment were enrolled from 29 intensive care units in 9 countries from November 11, 2010, to January 10, 2013. Final follow-up was completed on July 3, 2013, and data were assessed from February 1, 2014, to February 1, 2016. INTERVENTIONS: Blood sampling at 48 hours after the return of spontaneous circulation. MAINOUTCOMES AND MEASURES: The primary end point was poor neurologic outcomeat6 months (cerebral performance category score, 3 [severe neurologic sequelae], 4 [coma], or 5 [death]). The secondary end point was survival until the end of the trial. Circulating levels of miRNAs were measured by sequencing and polymerase chain reaction. RESULTS: Of the 579 patients (265 men [80.3%]; mean [SD] age, 63 [12] years), 304 patients (52.5%) hada poor neurologic outcomeat 6months. Inthe discovery phase with short RNA sequencing in 50 patients, the brain-enriched miR-124-3p level was identified as a candidate prognostic variable for neurologic outcomes. In the validation cohort of 529 patients, mean (SD) levels of miR-124-3p were higher in patients with a poor outcome (8408 [12 465] copies/μL) compared with patients with a good outcome (1842 [3025] copies/μL; P < .001). The miR-124-3p level was significantly associated with neurologic outcomes in the univariable analysis (odds ratio, 6.72; 95% CI, 4.53-9.97). In multivariable analyses using logistic regression, miR-124-3p levels were independently associated with neurologic outcomes (odds ratio, 1.62; 95% CI, 1.13-2.32). In Cox proportional hazards models, higher levels of miR-124-3p were significantly associated with lower survival (hazard ratio, 1.63; 95% CI, 1.37-1.93). CONCLUSIONS AND RELEVANCE: Levels of miR-124-3p can be used as prognostication tools for neurologic outcome and survival after out-of-hospital cardiac arrest. Thus, miRNA levels may aid in tailoring health care for patients with cardiac arrest.
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| 65. |
- Devaux, Yvan, et al.
(författare)
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Incremental value of circulating MiR-122-5P to predict outcome after out of hospital cardiac arrest
- 2017
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Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 7:10, s. 2555-2564
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Tidskriftsartikel (refereegranskat)abstract
- Rationale. The value of microRNAs (miRNAs) as biomarkers has been addressed in various clinical contexts. Initial studies suggested that miRNAs, such as the brain-enriched miR-124-3p, might improve outcome prediction after out-of-hospital cardiac arrest. The aim of this study is to determine the prognostic value of miR-122-5p in a large cohort of comatose survivors of out-of-hospital cardiac arrest. Methods. We analyzed 590 patients from the Targeted Temperature Management trial (TTM-trial). Circulating levels of miR-122-5p were measured in serum samples obtained 48 hours after return of spontaneous circulation. The primary end-point was poor neurological outcome at 6 months evaluated by the cerebral performance category score. The secondary end-point was survival at the end of the trial. Results. Forty-eight percent of patients had a poor neurological outcome at 6 months and 43% were dead at the end of the trial. Levels of miR-122-5p were lower in patients with poor neurological outcome compared to patients with good neurological outcome (p < 0.001), independently of targeted temperature management regimen. Levels of miR-122-5p were significant univariate predictors of neurological outcome (odds ratios (OR), 95% confidence intervals (CI): 0.71 [0.57-0.88]). In multivariable analyses, miR-122-5p was an independent predictor of neurological outcome and improved the predictive value of a clinical model including miR-124-3p (integrated discrimination improvement of 0.03 [0.02-0.04]). In Cox proportional hazards models, miR-122-5p was a significant predictor of survival at the end of the trial. Conclusion. Circulating levels of miR-122-5p improve the prediction of outcome after out-of-hospital cardiac arrest.
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| 66. |
- Devaux, Yvan, et al.
(författare)
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MicroRNAs: new biomarkers and therapeutic targets after cardiac arrest?
- 2015
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 19:1
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Forskningsöversikt (refereegranskat)abstract
- Despite advances in resuscitation medicine, including target temperature management as part of postcardiac arrest care, many patients will have a poor neurological outcome, most often resulting in death. It is a commonly held belief that the ability to prognosticate outcome at an early stage after cardiac arrest would allow subsequent health care delivery to be tailored to individual patients. However, currently available predictive methods and biomarkers lack sufficient accuracy and therefore cannot be generally recommended in clinical practice. MicroRNAs have recently emerged as potential biomarkers of cardiovascular diseases. While the biomarker value of microRNAs for myocardial infarction or heart failure has been extensively studied, less attention has been devoted to their prognostic value after cardiac arrest. This review highlights the recent discoveries suggesting that microRNAs may be useful both to predict outcome and to treat patients after cardiac arrest.
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| 67. |
- Didriksson, Ingrid, et al.
(författare)
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Increasing plasma calprotectin (S100A8/A9) is associated with 12-month mortality and unfavourable functional outcome in critically ill COVID-19 patients
- 2024
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Ingår i: Journal of Intensive Care. - 2052-0492. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Calprotectin (S100A8/A9) is a pro-inflammatory mediator primarily released from neutrophils. Previous studies have revealed associations between plasma calprotectin, disease severity and in-hospital mortality in unselected COVID-19 patients.OBJECTIVE: We aimed to assess whether plasma calprotectin dynamics during the first week of intensive care are associated with mortality and functional outcome in critically ill COVID-19 patients.METHODS: This prospective study included 498 COVID-19 patients admitted to six intensive care units (ICUs) in Sweden between May 2020 and May 2021. Blood samples were collected on ICU admission and on day 7. The primary outcome was 12-month mortality. Secondary outcomes were functional outcome of survivors at 3 and 12 months, and the need for invasive mechanical ventilation (IMV) or continuous renal replacement therapy (CRRT) during the ICU stay. Functional outcome was assessed by the Glasgow Outcome Scale Extended (GOSE, range 1-8, with < 5 representing an unfavourable outcome). Associations between plasma calprotectin and outcomes were examined in binary logistic regression analyses adjusted for age, sex, BMI, hypertension, smoking, and creatinine.RESULTS: High plasma calprotectin on admission and day 7 was independently associated with increased 12-month mortality. Increasing calprotectin from admission to day 7 was independently associated with higher mortality at 12 months [OR 2.10 (95% CI 1.18-3.74), p = 0.012], unfavourable functional outcome at 3 months [OR 2.53 (95% CI 1.07-6.10), p = 0.036], and the use of IMV [OR 2.23 (95% CI 1.10-4.53), p = 0.027)] and CRRT [OR 2.07 (95% CI 1.07-4.00), p = 0.031)]. A receiver operator characteristic (ROC) model including day 7 calprotectin and age was a good predictor of 12-month mortality [AUC 0.79 (95% CI 0.74-0.84), p < 0.001]. Day 7 calprotectin alone predicted an unfavourable functional outcome at 3 months [AUC 0.67 (95% CI 0.58-0.76), p < 0.001].CONCLUSION: In critically ill COVID-19 patients, increasing calprotectin levels after admission to the ICU are associated with 12-month mortality and unfavourable functional outcome in survivors. Monitoring plasma calprotectin dynamics in the ICU may be considered to evaluate prognosis in critical COVID-19.STUDY REGISTRATION: ClinicalTrials.gov Identifier: NCT04974775, registered April 28, 2020.
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| 68. |
- Didriksson, Ingrid, et al.
(författare)
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Intensive care unit burden is associated with increased mortality in critically ill COVID-19 patients
- 2023
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 67:3, s. 329-338
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Traditional models to predict intensive care outcomes do not perform well in COVID-19. We undertook a comprehensive study of factors affecting mortality and functional outcome after severe COVID-19.METHODS: In this prospective multicentre cohort study, we enrolled laboratory-confirmed, critically ill COVID-19 patients at six ICUs in the Skåne Region, Sweden, between May 11, 2020, and May 10, 2021. Demographics and clinical data were collected. ICU burden was defined as the total number of ICU-treated COVID-19 patients in the region on admission. Surviving patients had a follow-up at 90 days for assessment of functional outcome using the Glasgow Outcome Scale-Extended (GOSE), an ordinal scale (1-8) with GOSE ≥5 representing a favourable outcome. The primary outcome was 90-day mortality; the secondary outcome was functional outcome at 90 days.RESULTS: Among 498 included patients, 74% were male with a median age of 66 years and a median body mass index (BMI) of 30 kg/m 2 . Invasive mechanical ventilation was employed in 72%. Mortality in the ICU, in-hospital and at 90 days was 30%, 38% and 39%, respectively. Mortality increased markedly at age 60 and older. Increasing ICU burden was independently associated with a two-fold increase in mortality. Higher BMI was not associated with increased mortality. Besides age and ICU burden, smoking status, cortisone use, P a CO 2 >7 kPa, and inflammatory markers on admission were independent factors of 90-day mortality. Lower GOSE at 90 days was associated with a longer stay in the ICU. CONCLUSION: In critically ill COVID-19 patients, the 90-day mortality was 39% and increased considerably at age 60 or older. The ICU burden was associated with mortality, whereas a high BMI was not. A longer stay in the ICU was associated with unfavourable functional outcomes at 90 days.
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| 69. |
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| 70. |
- Dragancea, Irina, et al.
(författare)
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Outcome following postanoxic status epilepticus in patients with targeted temperature management after cardiac arrest.
- 2015
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Ingår i: Epilepsy & Behavior. - : Elsevier BV. - 1525-5069 .- 1525-5050. ; 49:Jun 24, s. 173-177
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Tidskriftsartikel (refereegranskat)abstract
- Postanoxic electrographic status epilepticus (ESE) is considered a predictor of poor outcome in resuscitated patients after cardiac arrest (CA). Observational data suggest that a subgroup of patients may have a good outcome. This study aimed to describe the prevalence of ESE and potential clinical and electrographic prognostic markers.
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