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- 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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| 2. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 3. |
- Storm, Christian, et al.
(författare)
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A survey on general and temperature management of post cardiac arrest patients in large teaching and university hospitals in 14 European countries-The SPAME trial results
- 2017
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 116, s. 84-90
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: International guidelines recommend a bundle of care, including targeted temperature management (TTM), in post cardiac arrest survivors. Aside from a few small surveys in different European countries, adherence to the European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) recommendations are unknown. Methods: This international European telephone survey was conducted to provide an overview of current clinical practice of post cardiac arrest management with a main focus on TTM. We targeted large teaching and university hospitals within Europe as leading facilities and key opinion leaders in the field of post cardiac arrest care. Selected national principal investigators conducted the survey, which was based on a predefined questionnaire, between December 2014 and March 2015, before the publication of the ERC Guidelines 2015. Results: The return rate was 94% from 268 participating intensive care units (ICU). The majority had a predefined standard operating procedure (SOP) protocol for post cardiac arrest patients. Altogether, 68% of the ICUs provided TTM at a target temperature of 32-34. °C for 24. h, and 33% had changed the target temperature to 36. °C. The minority provided a written SOP for neurological prognostication, which was generally initiated 72. h after return of spontaneous circulation (ROSC). Electroencephalography and somatosensory evoked potentials were used by most ICUs for early prognostication. Treating more than fifty patients a year was significantly associated with providing written SOPs for TTM and prognostication (p. <. 0.01), as well as the use of a computer feedback device (p = 0.03) for TTM. Conclusion: This international European telephone survey revealed a high rate of implementation of TTM in post cardiac arrest patients in university and teaching hospitals. Most participants also provided a SOP, but only a minority had a SOP for neurological prognostication.
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| 4. |
- Taccone, Fabio Silvio, et al.
(författare)
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Death after awakening from post-anoxic coma : The "best CPC" project
- 2019
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: In patients who recover consciousness after cardiac arrest (CA), a subsequent death from non-neurological causes may confound the assessment of long-term neurological outcome. We investigated the prevalence and causes of death after awakening (DAA) in a multicenter cohort of CA patients. Methods: Observational multicenter cohort study on patients resuscitated from CA in eight European intensive care units (ICUs) from January 2007 to December 2014. DAA during the hospital stay was extracted retrospectively from patient medical records. Demographics, comorbidities, initial CA characteristics, concomitant therapies, prognostic tests (clinical examination, electroencephalography (EEG), somatosensory evoked potentials (SSEPs)), and cause of death were identified. Results: From a total 4646 CA patients, 2478 (53%) died in-hospital, of whom 196 (4.2%; ranges 0.6-13.0%) had DAA. DAA was less frequent among out-of-hospital than in-hospital CA (82/2997 [2.7%] vs. 114/1649 [6.9%]; p < 0.001). Median times from CA to awakening and from awakening to death were 2 [1-5] and 9 [3-18] days, respectively. The main causes of DAA were multiple organ failure (n = 61), cardiogenic shock (n = 61), and re-arrest (n = 26). At day 3 from admission, results from EEG (n = 56) and SSEPs (n = 60) did not indicate poor outcome. Conclusions: In this large multicenter cohort, DAA was observed in 4.2% of non-survivors. Information on DAA is crucial since it may influence epidemiology and the design of future CA studies evaluating neuroprognostication and neuroprotection.
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