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- Blennow Nordström, Erik, et al.
(författare)
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Combined use of the Montreal Cognitive Assessment and Symbol Digit Modalities Test improves neurocognitive screening accuracy after cardiac arrest : A validation sub-study of the TTM2 trial
- 2024
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Ingår i: Resuscitation. - 0300-9572. ; 202
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To assess the merit of clinical assessment tools in a neurocognitive screening following out-of-hospital cardiac arrest (OHCA).Methods: The neurocognitive screening that was evaluated included the performance-based Montreal Cognitive Assessment (MoCA) and Symbol Digit Modalities Test (SDMT), the patient-reported Two Simple Questions (TSQ) and the observer-reported Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest (IQCODE-CA). These instruments were administered at 6-months in the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. We used a comprehensive neuropsychological test battery from a TTM2 trial sub-study as a gold standard to evaluate the sensitivity and specificity of the neurocognitive screening.Results: In our cohort of 108 OHCA survivors (median age = 62, 88% male), the most favourable cut-off scores were: MoCA < 26; SDMT z ≤ -1; IQCODE-CA ≥ 3.04. The MoCA (sensitivity 0.64, specificity 0.85) and SDMT (sensitivity 0.59, specificity 0.83) had a higher classification accuracy than the TSQ (sensitivity 0.28, specificity 0.74) and IQCODE-CA (sensitivity 0.42, specificity 0.60). When using the cut-points for MoCA or SDMT in combination to identify neurocognitive impairment, sensitivity improved (0.81, specificity 0.74), area under the curve = 0.77, 95% CI [0.69, 0.85]. The most common unidentified impairments were within the episodic memory and executive functions domains, with fewer false negative cases on the MoCA or SDMT combined.Conclusion: The MoCA and SDMT have acceptable diagnostic accuracy for screening for neurocognitive impairment in an OHCA population, and when used in combination the sensitivity improves. Patient and observer-reports correspond poorly with neurocognitive performance.ClinicalTrials.gov Identifier: NCT03543371.
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| 4. |
- Blennow Nordström, Erik, et al.
(författare)
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Neuropsychological outcome after cardiac arrest : results from a sub-study of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
- 2023
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Ingår i: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 27:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cognitive impairment is common following out-of-hospital cardiac arrest (OHCA), but the nature of the impairment is poorly understood. Our objective was to describe cognitive impairment in OHCA survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA.METHODS: This was a prospective case-control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. At approximately 7 months post-event, we administered an extensive neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes.RESULTS: Of 184 eligible OHCA survivors, 108 were included, with 92 MI controls enrolled. Amongst OHCA survivors, 29% performed z-score ≤ - 1 (at least borderline-mild impairment) in ≥ 2 cognitive domains, 14% performed z-score ≤ - 2 (major impairment) in ≥ 1 cognitive domain while 54% performed without impairment in any domain. Impairment was most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = - 0.37, 95% confidence intervals [- 0.61, - 0.12]), verbal (MD = - 0.34 [- 0.62, - 0.07]), and visual/constructive functions (MD = - 0.26 [- 0.47, - 0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, executive functions (MD = - 0.44 [- 0.82, - 0.06]) were also worse following OHCA. Diabetes, symptoms of anxiety, depression, and fatigue were significantly associated with worse cognitive performance.CONCLUSIONS: In our study population, cognitive impairment was generally mild following OHCA. OHCA survivors performed worse than MI controls in 3 of 6 domains. These results support current guidelines that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue.TRIAL REGISTRATION: ClinicalTrials.gov, NCT03543371. Registered 1 June 2018.
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| 5. |
- Blennow Nordström, Erik, et al.
(författare)
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Neuropsychological outcome after cardiac arrest : A prospective case control sub-study of the Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2)
- 2020
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA. Methods: This longitudinal multi-center clinical study is a sub-study of the TTM2-trial, in which a comprehensive neuropsychological examination is performed in addition to the main TTM2-trial neurocognitive screening. Approximately 7 and 24 months after OHCA, survivors at selected study sites are invited to a standardized assessment, including performance-based tests of cognition and questionnaires of emotional problems, fatigue, executive function and insomnia. At 1:1 ratio, a matched control group from a cohort of acute myocardial infarction (MI) patients is recruited to perform the same assessment. We aim to include 100 patients per group. Potential differences between the OHCA patients and the MI controls at 7 and 24 months will be analyzed with a linear regression, using composite z-scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions) as primary outcome measures. Results from OHCA survivors on the main TTM2-trial neurocognitive screening battery will be compared with neuropsychological test results at 7 months, using sensitivity and specificity analyses. Discussion: In this study we collect detailed information on cognitive impairment after OHCA and compare this to a control group of patients with acute MI. The validation of the TTM2 neurocognitive screening battery could justify its inclusion in routine follow-up. Our results may have a potential to impact on the design of future follow-up strategies and interventions after OHCA. Trial registration: ClinicalTrials.gov, NCT03543371. Registered 1 June 2018
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| 7. |
- Blennow Nordström, Erik, et al.
(författare)
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Serum neurofilament light levels are correlated to long-term neurocognitive outcome measures after cardiac arrest
- 2022
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Ingår i: Brain Injury. - : Informa UK Limited. - 0269-9052 .- 1362-301X. ; 36:6, s. 800-809
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Tidskriftsartikel (refereegranskat)abstract
- Objective To explore associations between four methods assessing long-term neurocognitive outcome after out-of-hospital cardiac arrest and early hypoxic-ischemic neuronal brain injury assessed by the biomarker serum neurofilament light (NFL), and to compare the agreement for the outcome methods. Methods An explorative post-hoc study was conducted on survivor data from the international Target Temperature Management after Out-of-hospital Cardiac Arrest trial, investigating serum NFL sampled 48/72-hours post-arrest and neurocognitive outcome 6 months post-arrest. Results Among the long-term surviving participants (N = 457), serum NFL (n = 384) was associated to all outcome instruments, also when controlling for demographic and cardiovascular risk factors. Associations between NFL and the patient-reported Two Simple Questions (TSQ) were however attenuated when adjusting for vitality and mental health. NFL predicted results on the outcome instruments to varying degrees, with an excellent area under the curve for the clinician-report Cerebral Performance Category (CPC 1-2: 0.90). Most participants were classified as CPC 1 (79%). Outcome instrument correlations ranged from small (Mini-Mental State Examination [MMSE]-TSQ) to strong (CPC-MMSE). Conclusions The clinician-reported CPC was mostly related to hypoxic-ischemic brain injury, but with a ceiling effect. These results may be useful when selecting methods and instruments for clinical follow-up models.
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| 8. |
- Bohm, Mattias, et al.
(författare)
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Caregiver burden and health-related quality of life amongst caregivers of out-of-hospital cardiac arrest survivors
- 2021
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Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 167:October, s. 118-127
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Tidskriftsartikel (refereegranskat)abstract
- Aims:To describe burden and health-related quality of life amongst caregivers of out-of-hospital cardiac arrest survivors and explore the potential association with cognitive function of the survivors. Caregivers of patients with ST-elevation myocardial infarction were used as controls.Methods:Data were collected from the cognitive substudy of the Targeted Temperature Management-trial. Caregiver burden was assessed with the 22-item Zarit Burden Interview, with scores <20 considered as no burden. Health-related quality of life was assessed with the SF-36v2 (R), with T scores 47-53 representing the norm. Cardiac arrest survivors were categorized based on the results from cognitive assessments as having "no cognitive impairment" or "cognitive impairment".Results:Follow-up 6 months post event was performed for caregivers of 272 cardiac arrest survivors and 108 matched myocardial infarction controls, included at an intended ratio of 2:1. In general, caregivers of cardiac arrest survivors and controls reported similar caregiver burden. The overall scores for quality of life were within normative levels and similar for caregivers of cardiac arrest survivors and control patients. Compared to those with no cognitive impairment, caregivers of cognitively impaired cardiac arrest survivors (n = 126) reported higher levels of burden (median 18 versus 8, p < 0.001) and worse quality of life in five of eight domains, particularly "Role-Emotional" (mean 45.7 versus 49.5, p = 0.002).Conclusions: In general, caregivers of cardiac arrest survivors and myocardial infarction controls reported similar levels of burden and quality of life. Cognitive outcome and functional dependency of the cardiac arrest survivor impact burden and quality of life of the caregiver.
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| 9. |
- Dankiewicz, Josef, et al.
(författare)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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| 10. |
- 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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