Publications by authors named "M Tiainen"

133 Publications

Haemodynamics and vasopressor support during prolonged targeted temperature management for 48 hours after out-of-hospital cardiac arrest: a post hoc substudy of a randomised clinical trial.

Eur Heart J Acute Cardiovasc Care 2020 Jun 17. Epub 2020 Jun 17.

Research Center for Emergency Medicine, Aarhus University Hospital and Aarhus University, Denmark.

Background: Comatose patients admitted after out-of-hospital cardiac arrest frequently experience haemodynamic instability and anoxic brain injury. Targeted temperature management is used for neuroprotection; however, targeted temperature management also affects patients' haemodynamic status. This study assessed the haemodynamic status of out-of-hospital cardiac arrest survivors during prolonged (48 hours) targeted temperature management at 33°C.

Methods: Analysis of haemodynamic and vasopressor data from 311 patients included in a randomised, clinical trial conducted in 10 European hospitals (the TTH48 trial). Patients were randomly allocated to targeted temperature management at 33°C for 24 (TTM24) or 48 (TTM48) hours. Vasopressor and haemodynamic data were reported hourly for 72 hours after admission. Vasopressor load was calculated as norepinephrine (µg/kg/min) plus dopamine(µg/kg/min/100) plus epinephrine (µg/kg/min).

Results: After 24 hours, mean arterial pressure (mean±SD) was 74±9 versus 75±9 mmHg (P=0.19), heart rate was 57±16 and 55±14 beats/min (P=0.18), vasopressor load was 0.06 (0.03-0.15) versus 0.08 (0.03-0.15) µg/kg/min (P=0.22) for the TTM24 and TTM48 groups, respectively. From 24 to 48 hours, there was no difference in mean arterial pressure (Pgroup=0.32) or lactate (Pgroup=0.20), while heart rate was significantly lower (average difference 5 (95% confidence interval 2-8) beats/min, Pgroup<0.0001) and vasopressor load was significantly higher in the TTM48 group (Pgroup=0.005). In a univariate Cox regression model, high vasopressor load was associated with mortality in univariate analysis (hazard ratio 1.59 (1.05-2.42) P=0.03), but not in multivariate analysis (hazard ratio 0.77 (0.46-1.29) P=0.33).

Conclusions: In this study, prolonged targeted temperature management at 33°C for 48 hours was associated with higher vasopressor requirement but no sign of any detrimental haemodynamic effects.
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http://dx.doi.org/10.1177/2048872620934305DOI Listing
June 2020

Effect of Nanoparticle Size in Pt/SiO Catalyzed Nitrate Reduction in Liquid Phase.

Nanomaterials (Basel) 2021 Jan 14;11(1). Epub 2021 Jan 14.

Environmental and Chemical Engineering Research Unit, University of Oulu, P.O. Box 4300, FI-90014 Oulu, Finland.

Effect of platinum nanoparticle size on catalytic reduction of nitrate in liquid phase was examined under ambient conditions by using hydrogen as a reducing agent. For the size effect study, Pt nanoparticles with sizes of 2, 4 and 8 nm were loaded silica support. TEM images of Pt nanoparticles showed that homogeneous morphologies as well as narrow size distributions were achieved during the preparation. All three catalysts showed high activity and were able to reduce nitrate below the recommended limit of 50 mg/L in drinking water. The highest catalytic activity was seen with 8 nm platinum; however, the product selectivity for N was highest with 4 nm platinum. In addition, the possibility of PVP capping agent acting as a promoter in the reaction is highlighted.
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http://dx.doi.org/10.3390/nano11010195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828658PMC
January 2021

Serum fibroblast growth factor 21 levels after out of hospital cardiac arrest are associated with neurological outcome.

Sci Rep 2021 Jan 12;11(1):690. Epub 2021 Jan 12.

Division of Intensive Care, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, PB 340, 00029, Helsinki, Finland.

Fibroblast growth factor (FGF) 21 is a marker associated with mitochondrial and cellular stress. Cardiac arrest causes mitochondrial stress, and we tested if FGF 21 would reflect the severity of hypoxia-reperfusion injury after cardiac arrest. We measured serum concentrations of FGF 21 in 112 patients on ICU admission and 24, 48 and 72 h after out-of-hospital cardiac arrest with shockable initial rhythm included in the COMACARE study (NCT02698917). All patients received targeted temperature management for 24 h. We defined 6-month cerebral performance category 1-2 as good and 3-5 as poor neurological outcome. We used samples from 40 non-critically ill emergency room patients as controls. We assessed group differences with the Mann Whitney U test and temporal differences with linear modeling with restricted maximum likelihood estimation. We used multivariate logistic regression to assess the independent predictive value of FGF 21 concentration for neurologic outcome. The median (inter-quartile range, IQR) FGF 21 concentration was 0.25 (0.094-0.91) ng/ml in controls, 0.79 (0.37-1.6) ng/ml in patients at ICU admission (P < 0.001 compared to controls) and peaked at 48 h [1.2 (0.46-2.5) ng/ml]. We found no association between arterial blood oxygen partial pressure and FGF 21 concentrations. We observed with linear modeling an effect of sample timepoint (F 5.6, P < 0.01), poor neurological outcome (F 6.1, P = 0.01), and their interaction (F 3.0, P = 0.03), on FGF 21 concentration. In multivariate logistic regression analysis, adjusting for relevant clinical covariates, higher average FGF 21 concentration during the first 72 h was independently associated with poor neurological outcome (odds ratio 1.60, 95% confidence interval 1.10-2.32). We conclude that post cardiac arrest patients experience cellular and mitochondrial stress, reflected as a systemic FGF 21 response. This response is higher with a more severe hypoxic injury but it is not exacerbated by hyperoxia.
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http://dx.doi.org/10.1038/s41598-020-80086-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804444PMC
January 2021

Nursing professionals' experiences of person-centred practices in hospital settings.

Scand J Caring Sci 2020 Nov 6. Epub 2020 Nov 6.

Faculty of Social Sciences, Health Sciences, Tampere University, Tampere, Finland.

Background: Person-centred culture has been studied very little in Scandinavian Countries, yet it significantly affects in the care experiences of patients and staff. Current research indicates there are many factors restricting or enabling person-centred care in the hospital setting.

Aim: The purpose of this study was to describe person-centred practice in hospital settings and the factors associated with it.

Method: Data were collected from nursing professionals (N = 276) in a purposefully selected city hospital in one hospital district in Finland. The professionals worked in inpatient wards that had the average duration of treatment period more than one day. The Person-Centred Practice Inventory-Staff (PCPI-S) instrument was used to obtain data via an electronic questionnaire. Data were analysed statistically.

Results: A 30% response rate was achieved (n = 82). Person-centred practice was described in positive ways. Nursing professionals' assessments of the implementation of person-centred practice were fairly positive, prerequisites (mean = 3.93, SD = 0.40), the care environment (mean = 3.64, SD = 0.50) and the care process (mean = 3.98, SD = 0.42). There were a few background factors such as the nursing professionals' age, job title, work experience in current unit, employment relationship and the number of nursing professionals in the ward that were associated with how they assessed the prerequisites of person-centred practice. Nursing professionals' demographic variables such as their job title and working experience in nursing associated with how they assessed the implementation of person-centredness in the care environment and the care process.

Conclusions: Nursing professionals have the ability to implement person-centred practice. However, newly graduated or less experienced nursing professionals need support to explore person-centredness in their work.
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http://dx.doi.org/10.1111/scs.12925DOI Listing
November 2020

Tranexamic acid in patients with intracerebral haemorrhage (STOP-AUST): a multicentre, randomised, placebo-controlled, phase 2 trial.

Lancet Neurol 2020 12 28;19(12):980-987. Epub 2020 Oct 28.

Departments of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia.

Background: Despite intracerebral haemorrhage causing 5% of deaths worldwide, few evidence-based therapeutic strategies other than stroke unit care exist. Tranexamic acid decreases haemorrhage in conditions such as acute trauma and menorrhoea. We aimed to assess whether tranexamic acid reduces intracerebral haemorrhage growth in patients with acute intracerebral haemorrhage.

Methods: We did a prospective, double-blind, randomised, placebo-controlled, investigator-led, phase 2 trial at 13 stroke centres in Australia, Finland, and Taiwan. Patients were eligible if they were aged 18 years or older, had an acute intracerebral haemorrhage fulfilling clinical criteria (eg, Glasgow Coma Scale score of >7, intracerebral haemorrhage volume <70 mL, no identified or suspected secondary cause of intracerebral haemorrhage, no thrombotic events within the previous 12 months, no planned surgery in the next 24 h, and no use of anticoagulation), had contrast extravasation on CT angiography (the so-called spot sign), and were treatable within 4·5 h of symptom onset and within 1 h of CT angiography. Patients were randomly assigned (1:1) to receive either 1 g of intravenous tranexamic acid over 10 min followed by 1 g over 8 h or matching placebo, started within 4·5 h of symptom onset. Randomisation was done using a centralised web-based procedure with randomly permuted blocks of varying size. All patients, investigators, and staff involved in patient management were masked to treatment. The primary outcome was intracerebral haemorrhage growth (>33% relative or >6 mL absolute) at 24 h. The primary and safety analyses were done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT01702636).

Findings: Between March 1, 2013, and Aug 13, 2019, we enrolled and randomly assigned 100 participants to the tranexamic acid group (n=50) or the placebo group (n=50). Median age was 71 years (IQR 57-79) and median intracerebral haemorrhage volume was 14·6 mL (7·9-32·7) at baseline. The primary outcome was not different between the two groups: 26 (52%) patients in the placebo group and 22 (44%) in the tranexamic acid group had intracerebral haemorrhage growth (odds ratio [OR] 0·72 [95% CI 0·32-1·59], p=0·41). There was no evidence of a difference in the proportions of patients who died or had thromboembolic complications between the groups: eight (16%) in the placebo group vs 13 (26%) in the tranexamic acid group died and two (4%) vs one (2%) had thromboembolic complications. None of the deaths was considered related to study medication.

Interpretation: Our study does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth, although the treatment was safe with no increase in thromboembolic complications. Larger trials of tranexamic acid, with simpler recruitment methods and an earlier treatment window, are justified.

Funding: National Health and Medical Research Council, Royal Melbourne Hospital Foundation.
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http://dx.doi.org/10.1016/S1474-4422(20)30369-0DOI Listing
December 2020

Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial.

Intensive Care Med 2021 Jan 27;47(1):39-48. Epub 2020 Aug 27.

Department of Emergency Care and Services, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Purpose: Neurofilament light (NfL) is a biomarker reflecting neurodegeneration and acute neuronal injury, and an increase is found following hypoxic brain damage. We assessed the ability of plasma NfL to predict outcome in comatose patients after out-of-hospital cardiac arrest (OHCA). We also compared plasma NfL concentrations between patients treated with two different targets of arterial carbon dioxide tension (PaCO), arterial oxygen tension (PaO), and mean arterial pressure (MAP).

Methods: We measured NfL concentrations in plasma obtained at intensive care unit admission and at 24, 48, and 72 h after OHCA. We assessed neurological outcome at 6 months and defined a good outcome as Cerebral Performance Category (CPC) 1-2 and poor outcome as CPC 3-5.

Results: Six-month outcome was good in 73/112 (65%) patients. Forty-eight hours after OHCA, the median NfL concentration was 19 (interquartile range [IQR] 11-31) pg/ml in patients with good outcome and 2343 (587-5829) pg/ml in those with poor outcome, p < 0.001. NfL predicted poor outcome with an area under the receiver operating characteristic curve (AUROC) of 0.98 (95% confidence interval [CI] 0.97-1.00) at 24 h, 0.98 (0.97-1.00) at 48 h, and 0.98 (0.95-1.00) at 72 h. NfL concentrations were lower in the higher MAP (80-100 mmHg) group than in the lower MAP (65-75 mmHg) group at 48 h (median, 23 vs. 43 pg/ml, p = 0.04). PaCO and PaO targets did not associate with NfL levels.

Conclusions: NfL demonstrated excellent prognostic accuracy after OHCA. Higher MAP was associated with lower NfL concentrations.
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http://dx.doi.org/10.1007/s00134-020-06218-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782453PMC
January 2021

Optimum Blood Pressure in Patients With Shock After Acute Myocardial Infarction and Cardiac Arrest.

J Am Coll Cardiol 2020 08;76(7):812-824

Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Emergency Medicine and Services, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: In patients with shock after acute myocardial infarction (AMI), the optimal level of pharmacologic support is unknown. Whereas higher doses may increase myocardial oxygen consumption and induce arrhythmias, diastolic hypotension may reduce coronary perfusion and increase infarct size.

Objectives: This study aimed to determine the optimal mean arterial pressure (MAP) in patients with AMI and shock after cardiac arrest.

Methods: This study used patient-level pooled analysis of post-cardiac arrest patients with shock after AMI randomized in the Neuroprotect (Neuroprotective Goal Directed Hemodynamic Optimization in Post-cardiac Arrest Patients; NCT02541591) and COMACARE (Carbon Dioxide, Oxygen and Mean Arterial Pressure After Cardiac Arrest and Resuscitation; NCT02698917) trials who were randomized to MAP 65 mm Hg or MAP 80/85 to 100 mm Hg targets during the first 36 h after admission. The primary endpoint was the area under the 72-h high-sensitivity troponin-T curve.

Results: Of 235 patients originally randomized, 120 patients had AMI with shock. Patients assigned to the higher MAP target (n = 58) received higher doses of norepinephrine (p = 0.004) and dobutamine (p = 0.01) and reached higher MAPs (86 ± 9 mm Hg vs. 72 ± 10 mm Hg, p < 0.001). Whereas admission hemodynamics and angiographic findings were all well-balanced and revascularization was performed equally effective, the area under the 72-h high-sensitivity troponin-T curve was lower in patients assigned to the higher MAP target (median: 1.14 μg.72 h/l [interquartile range: 0.35 to 2.31 μg.72 h/l] vs. median: 1.56 μg.72 h/l [interquartile range: 0.61 to 4.72 μg. 72 h/l]; p = 0.04). Additional pharmacologic support did not increase the risk of a new cardiac arrest (p = 0.88) or atrial fibrillation (p = 0.94). Survival with good neurologic outcome at 180 days was not different between both groups (64% vs. 53%, odds ratio: 1.55; 95% confidence interval: 0.74 to 3.22).

Conclusions: In post-cardiac arrest patients with shock after AMI, targeting MAP between 80/85 and 100 mm Hg with additional use of inotropes and vasopressors was associated with smaller myocardial injury.
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http://dx.doi.org/10.1016/j.jacc.2020.06.043DOI Listing
August 2020

Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry.

Stroke 2020 09 9;51(9):e254-e258. Epub 2020 Jul 9.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, United Kingdom (G.Y.H.L.).

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), =0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], <0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.
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http://dx.doi.org/10.1161/STROKEAHA.120.031208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359900PMC
September 2020

Effect of haemoglobin levels on outcome in intravenous thrombolysis-treated stroke patients.

Eur Stroke J 2020 Jun 13;5(2):138-147. Epub 2019 Nov 13.

Stroke Center and Department of Neurology, University Hospital Basel and University of Basel, Basel, Switzerland.

Introduction: Alterations in haemoglobin levels are frequent in stroke patients. The prognostic meaning of anaemia and polyglobulia on outcomes in patients treated with intravenous thrombolysis is ambiguous.

Patients And Methods: In this prospective multicentre, intravenous thrombolysis register-based study, we compared haemoglobin levels on hospital admission with three-month poor outcome (modified Rankin Scale 3-6), mortality and symptomatic intracranial haemorrhage (European Cooperative Acute Stroke Study II-criteria (ECASS-II-criteria)). Haemoglobin level was used as continuous and categorical variable distinguishing anaemia (female: <12 g/dl; male: <13 g/dl) and polyglobulia (female: >15.5 g/dl; male: >17 g/dl). Anaemia was subdivided into mild and moderate/severe (female/male: <11 g/dl). Normal haemoglobin level (female: 12.0-15.5 g/dl, male: 13.0-17.0 g/dl) served as reference group. Unadjusted and adjusted odds ratios with 95% confidence intervals were calculated with logistic regression models.

Results: Among 6866 intravenous thrombolysis-treated stroke patients, 5448 (79.3%) had normal haemoglobin level, 1232 (17.9%) anaemia - of those 903 (13.2%) had mild and 329 (4.8%) moderate/severe anaemia - and 186 (2.7%) polyglobulia. Anaemia was associated with poor outcome (OR 1.25 (1.05-1.48)) and mortality (OR 1.58 (1.27-1.95)). In anaemia subgroups, both mild and moderate/severe anaemia independently predicted poor outcome (OR 1.29 (1.07-1.55) and 1.48 (1.09-2.02)) and mortality (OR 1.45 (1.15-1.84) and OR 2.00 (1.46-2.75)). Each haemoglobin level decrease by 1 g/dl independently increased the risk of poor outcome (OR 1.07 (1.02-1.11)) and mortality (OR 1.08 (1.02-1.15)). Anaemia was not associated with occurrence of symptomatic intracranial haemorrhage. Polyglobulia did not change any outcome.

Discussion: The more severe the anaemia, the higher the probability of poor outcome and death. Severe anaemia might be a target for interventions in hyperacute stroke.

Conclusion: Anaemia on admission, but not polyglobulia, is a strong and independent predictor of poor outcome and mortality in intravenous thrombolysis-treated stroke patients.
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http://dx.doi.org/10.1177/2396987319889468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313367PMC
June 2020

Association of prestroke metformin use, stroke severity, and thrombolysis outcome.

Neurology 2020 07 29;95(4):e362-e373. Epub 2020 Jun 29.

From the Department of Neurology (L.P.W., R.W., A.R.L., S.W.), University Hospital Zurich; Epidemiology, Biostatistics and Prevention Institute, Department of Biostatistics (U.H., K.S.), University of Zurich, Switzerland; Department of Neurology (C.H., P.R.), University Hospital Heidelberg, Germany; Department of Neurology (S.C., N.M.-M., M.T.), University of Helsinki and Helsinki University Hospital, Finland; Department of Neurology and Center for Stroke Research (C.H.N., J.F.S., H.E.), Charité University Hospital, Berlin, Germany; Stroke Center and Neurology (A.A.P., C.T., H.G., S.T.E.), University Hospital Basel and University Basel; Department of Neurology (A.E., P.M.), University Hospital Lausanne; Department of Neurology (M.R.H., M.A.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology and Stroke Center (A.Z.), IRCCS Istituto delle Scienze Neurologiche di Bologna, Maggiore Hospital; Stroke Unit (L.V.), Department of Neuroscience, S'Agostino-Estense Hospital, Modena University Hospital, Italy; Department of Neurology (J.M.C., A.E.G., P.N.), Amsterdam University Medical Centers (AUMC), Location AMC, University of Amsterdam, the Netherlands; Neurology Clinic Belgrade (V.P., D.R.J.), Clinical Centre of Serbia; Medical Faculty (D.R.J.), University of Belgrade, Serbia; Department of Neurology (Y.B., C.B.), University Hospital of Dijon, University of Burgundy; Department of Neurology (G.T., P.S.), Sainte-Anne Hospital, Paris, France; Department of Clinical and Experimental Sciences (A.P.), Neurology Clinic, University of Brescia; Stroke Unit (M.M.), ASST Spedali Civili, Brescia, Italy; Department of Neurology (D.L., S.G.), University Hospital of Lille, France; Department of Neurology (M.J.S., G.K.), St. Gallen Cantonal Hospital, Switzerland; Department of Neurology (T.T.), Sahlgrenska University Hospital; Department of Clinical Neurosciences (T.T.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation Basel, Felix Platter Hospital, University of Basel, Switzerland.

Objective: To evaluate whether pretreatment with metformin (MET) is associated with less stroke severity and better outcome after IV thrombolysis (IVT), we analyzed a cohort of 1,919 patients with stroke with type 2 diabetes mellitus in a multicenter exploratory analysis.

Methods: Data from patients with diabetes and ischemic stroke treated with IVT were collected within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration. We applied propensity score matching (PSM) to obtain balanced baseline characteristics of patients treated with and without MET.

Results: Of 1,919 patients with stroke with type 2 diabetes who underwent IVT, 757 (39%) had received MET before stroke (MET+), whereas 1,162 (61%) had not (MET-). MET+ patients were younger with a male preponderance. Hypercholesterolemia and pretreatment with statins, antiplatelets, or antihypertensives were more common in the MET+ group. After PSM, the 2 groups were well balanced with respect to demographic and clinical aspects. Stroke severity on admission (NIH Stroke Scale 10.0 ± 6.7 vs 11.3 ± 6.5), 3-month degree of independence on modified Rankin Scale (2 [interquartile range (IQR) 1.0-4.0] vs 3 [IQR 1.0-4.0]), as well as mortality (12.5% vs 18%) were significantly lower in the MET+ group. The frequency of symptomatic intracerebral hemorrhages did not differ between groups. HbA1c levels were well-balanced between the groups.

Conclusions: Patients with stroke and diabetes on treatment with MET receiving IVT had less severe strokes on admission and a better functional outcome at 3 months. This suggests a protective effect of MET resulting in less severe strokes as well as beneficial thrombolysis outcome.
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http://dx.doi.org/10.1212/WNL.0000000000009951DOI Listing
July 2020

The Definition of Informatics Competencies in Finnish Healthcare and Social Welfare Education.

Stud Health Technol Inform 2020 Jun;270:1143-1147

Laurea University of Applied Sciences, Espoo, Finland.

Finland is a world leader in the use of public electronic services. Continuous improvement to competencies is a prerequisite for the success of digitalisation in the service development sector. The increasing use of information technology in health and social care needs to be taken into account in the education of the health and social care sector work force. The mandate of the national SotePeda 24/7 project is to identify and define the informatics competencies required for multidisciplinary education of this sector in Finland. The project has adapted international recommendations for use in the national context. The national recommendation covers 12 areas of competency and related content. In addition to defining competencies, the project has produced a toolbox of materials for use by educators of these topics in universities that cover applied sciences and lifelong learning. The results of the project are expected to significantly improve the preparedness of graduating health and social care and related engineering and business sector students to make full use information technology, all of which benefits the national health and social welfare system.
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http://dx.doi.org/10.3233/SHTI200341DOI Listing
June 2020

Haemodynamics and vasopressor support during prolonged targeted temperature management for 48 hours after out-of-hospital cardiac arrest: a post hoc substudy of a randomised clinical trial.

Eur Heart J Acute Cardiovasc Care 2020 Jun 17:2048872620934305. Epub 2020 Jun 17.

Research Center for Emergency Medicine, Aarhus University Hospital and Aarhus University, Denmark.

Background: Comatose patients admitted after out-of-hospital cardiac arrest frequently experience haemodynamic instability and anoxic brain injury. Targeted temperature management is used for neuroprotection; however, targeted temperature management also affects patients' haemodynamic status. This study assessed the haemodynamic status of out-of-hospital cardiac arrest survivors during prolonged (48 hours) targeted temperature management at 33°C.

Methods: Analysis of haemodynamic and vasopressor data from 311 patients included in a randomised, clinical trial conducted in 10 European hospitals (the TTH48 trial). Patients were randomly allocated to targeted temperature management at 33°C for 24 (TTM24) or 48 (TTM48) hours. Vasopressor and haemodynamic data were reported hourly for 72 hours after admission. Vasopressor load was calculated as norepinephrine (µg/kg/min) plus dopamine(µg/kg/min/100) plus epinephrine (µg/kg/min).

Results: After 24 hours, mean arterial pressure (mean±SD) was 74±9 versus 75±9 mmHg (=0.19), heart rate was 57±16 and 55±14 beats/min (=0.18), vasopressor load was 0.06 (0.03-0.15) versus 0.08 (0.03-0.15) µg/kg/min (=0.22) for the TTM24 and TTM48 groups, respectively. From 24 to 48 hours, there was no difference in mean arterial pressure (=0.32) or lactate (=0.20), while heart rate was significantly lower (average difference 5 (95% confidence interval 2-8) beats/min, <0.0001) and vasopressor load was significantly higher in the TTM48 group (=0.005). In a univariate Cox regression model, high vasopressor load was associated with mortality in univariate analysis (hazard ratio 1.59 (1.05-2.42) =0.03), but not in multivariate analysis (hazard ratio 0.77 (0.46-1.29) =0.33).

Conclusions: In this study, prolonged targeted temperature management at 33°C for 48 hours was associated with higher vasopressor requirement but no sign of any detrimental haemodynamic effects.
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http://dx.doi.org/10.1177/2048872620934305DOI Listing
June 2020

European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousness.

Eur J Neurol 2020 05 23;27(5):741-756. Epub 2020 Feb 23.

Coma Science Group, GIGA Consciousness, University and University Hospital of Liège, Liège, Belgium.

Background And Purpose: Patients with acquired brain injury and acute or prolonged disorders of consciousness (DoC) are challenging. Evidence to support diagnostic decisions on coma and other DoC is limited but accumulating. This guideline provides the state-of-the-art evidence regarding the diagnosis of DoC, summarizing data from bedside examination techniques, functional neuroimaging and electroencephalography (EEG).

Methods: Sixteen members of the European Academy of Neurology (EAN) Scientific Panel on Coma and Chronic Disorders of Consciousness, representing 10 European countries, reviewed the scientific evidence for the evaluation of coma and other DoC using standard bibliographic measures. Recommendations followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The guideline was endorsed by the EAN.

Results: Besides a comprehensive neurological examination, the following suggestions are made: probe for voluntary eye movements using a mirror; repeat clinical assessments in the subacute and chronic setting, using the Coma Recovery Scale - Revised; use the Full Outline of Unresponsiveness score instead of the Glasgow Coma Scale in the acute setting; obtain clinical standard EEG; search for sleep patterns on EEG, particularly rapid eye movement sleep and slow-wave sleep; and, whenever feasible, consider positron emission tomography, resting state functional magnetic resonance imaging (fMRI), active fMRI or EEG paradigms and quantitative analysis of high-density EEG to complement behavioral assessment in patients without command following at the bedside.

Conclusions: Standardized clinical evaluation, EEG-based techniques and functional neuroimaging should be integrated for multimodal evaluation of patients with DoC. The state of consciousness should be classified according to the highest level revealed by any of these three approaches.
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http://dx.doi.org/10.1111/ene.14151DOI Listing
May 2020

Rivaroxaban versus aspirin for secondary prevention of ischaemic stroke in patients with cancer: a subgroup analysis of the NAVIGATE ESUS randomized trial.

Eur J Neurol 2020 05 11;27(5):841-848. Epub 2020 Mar 11.

Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.

Background And Purpose: Cancer is a frequent finding in ischaemic stroke patients. The frequency of cancer amongst participants in the NAVIGATE ESUS randomized trial and the distribution of outcome events during treatment with aspirin and rivaroxaban were investigated.

Methods: Trial participation required a recent embolic stroke of undetermined source. Patients' history of cancer was recorded at the time of study entry. During a mean follow-up of 11 months, the effects of aspirin and rivaroxaban treatment on recurrent ischaemic stroke, major bleeding and all-cause mortality were compared between patients with cancer and patients without cancer.

Results: Amongst 7213 randomized patients, 543 (7.5%) had cancer. Of all patients, 3609 were randomized to rivaroxaban [254 (7.0%) with cancer] and 3604 patients to aspirin [289 (8.0%) with cancer]. The annual rate of recurrent ischaemic stroke was 4.5% in non-cancer patients in the rivaroxaban arm and 4.6% in the aspirin arm [hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.78-1.24]. In cancer patients, the rate of recurrent ischaemic stroke was 7.7% in the rivaroxaban arm and 5.4% in the aspirin arm (HR 1.43, 95% CI 0.71-2.87). Amongst cancer patients, the annual rate of major bleeds was non-significantly higher for rivaroxaban than aspirin (2.9% vs. 1.1%; HR 2.57, 95% CI 0.67-9.96; P for interaction 0.95). All-cause mortality was similar in both groups.

Conclusions: Our exploratory analyses show that patients with embolic stroke of undetermined source and a history of cancer had similar rates of recurrent ischaemic strokes and all-cause mortality during aspirin and rivaroxaban treatments and that aspirin appeared safer than rivaroxaban in cancer patients regarding major bleeds. www.clinicaltrials.gov (NCT02313909).
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http://dx.doi.org/10.1111/ene.14172DOI Listing
May 2020

Metabolic Profiles Help Discriminate Mild Cognitive Impairment from Dementia Stage in Alzheimer's Disease.

J Alzheimers Dis 2020 ;74(1):277-286

Institute of Clinical Medicine - Neurology, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.

Accurate differentiation between neurodegenerative diseases is developing quickly and has reached an effective level in disease recognition. However, there has been less focus on effectively distinguishing the prodromal state from later dementia stages due to a lack of suitable biomarkers. We utilized the Disease State Index (DSI) machine learning classifier to see how well quantified metabolomics data compares to clinically used cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD). The metabolic profiles were quantified for 498 serum and CSF samples using proton nuclear magnetic resonance spectroscopy. The patient cohorts in this study were dementia (with a clinical AD diagnosis) (N = 359), mild cognitive impairment (MCI) (N = 96), and control patients with subjective memory complaints (N = 43). DSI classification was conducted for MCI (N = 51) and dementia (N = 214) patients with low CSF amyloid-β levels indicating AD pathology and controls without such amyloid pathology (N = 36). We saw that the conventional CSF markers of AD were better at classifying controls from both dementia and MCI patients. However, quantified metabolic subclasses were more effective in classifying MCI from dementia. Our results show the consistent effectiveness of traditional CSF biomarkers in AD diagnostics. However, these markers are relatively ineffective in differentiating between MCI and the dementia stage, where the quantified metabolomics data provided significant benefit.
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http://dx.doi.org/10.3233/JAD-191226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175942PMC
January 2020

Hypothermic to ischemic ratio and mortality in post-cardiac arrest patients.

Acta Anaesthesiol Scand 2020 04 26;64(4):546-555. Epub 2019 Dec 26.

Research Center for Emergency Medicine, Department of Emergency Medicine and Department of Clinical Medicine, Aarhus University Hospital and Aarhus University, Aarhus, Denmark.

Background: We studied the associations between ischemia and hypothermia duration, that is, the hypothermic to ischemic ratio (H/I ratio), with mortality in patients included in a trial on two durations of targeted temperature management (TTM) at 33°C.

Methods: The TTH48 (NCT01689077) trial compared 24 and 48 hours of TTM in patients after cardiac arrest. We calculated the hypothermia time from return of spontaneous circulation (ROSC) until the patient reached 37°C after TTM and the ischemic time from CA to ROSC. We compared continuous variables with the Mann-Whitney U test. Using COX regression, we studied the independent association of the logarithmically transformed H/I ratio and time to death as well as interaction between time to ROSC, hypothermia duration, and intervention group. We visualized the predictive ability of variables with receiver operating characteristic curve analysis.

Results: Of the 338 patients, 237 (70%) survived for 6 months. The H/I ratio was 155 (IQR 111-238) in survivors and 114 (IQR 80-169) in non-survivors (P < .001). In a Cox regression model including factors associated with outcome in univariate analysis, the logarithmically transformed H/I ratio was a significant predictor of outcome (hazard ratio 0.52 (0.37-0.72, P = .001)). After removing an outlier, we found no interaction between time to ROSC and intervention group (P = .55) or hypothermia duration in quartiles (P = .07) with mortality. There was no significant difference in the area under the curve (AUC) between time to ROSC and H/I ratio (ΔAUC 0.03 95% CI -0.006-0.07, P = .10).

Conclusions: We did not find any consistent evidence of a modification of the effect of TTM based on ischemia duration.
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http://dx.doi.org/10.1111/aas.13528DOI Listing
April 2020

Low Serum High-Density Lipoprotein Cholesterol Levels Associate with the C9orf72 Repeat Expansion in Frontotemporal Lobar Degeneration Patients.

J Alzheimers Dis 2019 ;72(1):127-137

Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland.

Decreased levels of serum high-density lipoprotein (HDL) cholesterol have previously been linked to systemic inflammation and neurodegenerative diseases, such as Alzheimer's disease. Here, we aimed to analyze the lipoprotein profile and inflammatory indicators, the high-sensitivity C-reactive peptide (hs-CRP) and glycoprotein acetyls (GlycA), in sporadic and C9orf72 repeat expansion-associated frontotemporal lobar degeneration (FTLD) patients. The C9orf72 hexanucleotide repeat expansion is the most frequent genetic etiology underlying FTLD. The concentrations of different lipid measures in the sera of 67 FTLD patients (15 C9orf72 repeat expansion carriers), including GlycA, were analyzed by nuclear magnetic resonance spectroscopy. To verify the state of systemic inflammation, hs-CRP was also quantified from patient sera. We found that the total serum HDL concentration was decreased in C9orf72 repeat expansion carriers when compared to non-carriers. Moreover, decreased concentrations of HDL particles of different sizes and subclass were consistently observed. No differences were detected in the very low- and low-density lipoprotein subclasses between the C9orf72 repeat expansion carriers and non-carriers. Furthermore, hs-CRP and GlycA levels did not differ between the C9orf72 repeat expansion carriers and non-carriers. In conclusion, the HDL-related changes were linked with C9orf72 repeat expansion associated FTLD but were not seen to associate with systemic inflammation. The underlying reason for the HDL changes remains unclear.
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http://dx.doi.org/10.3233/JAD-190132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839456PMC
November 2020

Connecting directional limb movements to vowel fronting and backing.

Neurosci Lett 2019 10 22;711:134457. Epub 2019 Aug 22.

Phonetics and speech synthesis research group, Department of Digital Humanities, University of Helsinki, Unioninkatu 40, 00014, Finland. Electronic address:

It has been shown recently that when participants are required to pronounce a vowel at the same time with the hand movement, the vocal and manual responses are facilitated when a front vowel is produced with forward-directed hand movements and a back vowel is produced with backward-directed hand movements. This finding suggests a coupling between spatial programing of articulatory tongue movements and hand movements. The present study revealed that the same effect can be also observed in relation to directional leg movements. The study suggests that the effect operates within the common directional processes of movement planning including at least tongue, hand and leg movements, and these processes might contribute sound-to-meaning mappings to the semantic concepts of 'forward' and 'backward'.
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http://dx.doi.org/10.1016/j.neulet.2019.134457DOI Listing
October 2019

Total liver phosphatidylcholine content associates with non-alcoholic steatohepatitis and glycine N-methyltransferase expression.

Liver Int 2019 10 8;39(10):1895-1905. Epub 2019 Jul 8.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.

Background & Aims: Alterations in liver phosphatidylcholine (PC) metabolism have been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Although genetic variation in the phosphatidylethanolamine N-methyltransferase (PEMT) enzyme synthesizing PC has been associated with disease, the functional mechanism linking PC metabolism to the pathogenesis of non-alcoholic steatohepatitis (NASH) remains unclear.

Methods: Serum PC levels and liver PC contents were measured using proton nuclear magnetic resonance (NMR) spectroscopy in 169 obese individuals [age 46.6 ± 10 (mean ± SD) years, BMI 43.3 ± 6 kg/m , 53 men and 116 women] with histological assessment of NAFLD; 106 of these had a distinct liver phenotype. All subjects were genotyped for PEMT rs7946 and liver mRNA expression of PEMT and glycine N-methyltransferase (GNMT) was analysed.

Results: Liver PC content was lower in those with NASH (P = 1.8 x 10 ) while serum PC levels did not differ between individuals with NASH and normal liver (P = 0.591). Interestingly, serum and liver PC did not correlate (r  = -0.047, P = 0.557). Serum PC and serum cholesterol levels correlated strongly (r  = 0.866, P = 7.1 x 10 ), while liver PC content did not correlate with serum cholesterol (r  = 0.065, P = 0.413). Neither PEMT V175M genotype nor PEMT expression explained the association between liver PC content and NASH. Instead, liver GNMT mRNA expression was decreased in those with NASH (P = 3.8 x 10 ) and correlated with liver PC content (r  = 0.265, P = 0.001).

Conclusions: Decreased liver PC content in individuals with the NASH is independent of PEMT V175M genotype and could be partly linked to decreased GNMT expression.
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http://dx.doi.org/10.1111/liv.14174DOI Listing
October 2019

Near-infrared spectroscopy after out-of-hospital cardiac arrest.

Crit Care 2019 05 14;23(1):171. Epub 2019 May 14.

Department of Emergency Medicine and Services, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Cerebral hypoperfusion may aggravate neurological damage after cardiac arrest. Near-infrared spectroscopy (NIRS) provides information on cerebral oxygenation but its relevance during post-resuscitation care is undefined. We investigated whether cerebral oxygen saturation (rSO) measured with NIRS correlates with the serum concentration of neuron-specific enolase (NSE), a marker of neurological injury, and with clinical outcome in out-of-hospital cardiac arrest (OHCA) patients.

Methods: We performed a post hoc analysis of a randomised clinical trial (COMACARE, NCT02698917) comparing two different levels of carbon dioxide, oxygen and arterial pressure after resuscitation from OHCA with ventricular fibrillation as the initial rhythm. We measured rSO in 118 OHCA patients with NIRS during the first 36 h of intensive care. We determined the NSE concentrations from serum samples at 48 h after cardiac arrest and assessed neurological outcome with the Cerebral Performance Category (CPC) scale at 6 months. We evaluated the association between rSO and serum NSE concentrations and the association between rSO and good (CPC 1-2) and poor (CPC 3-5) neurological outcome.

Results: The median (inter-quartile range (IQR)) NSE concentration at 48 h was 17.5 (13.4-25.0) μg/l in patients with good neurological outcome and 35.2 (22.6-95.8) μg/l in those with poor outcome, p < 0.001. We found no significant correlation between median rSO and NSE at 48 h, r = - 0.08, p = 0.392. The median (IQR) rSO during the first 36 h of intensive care was 70.0% (63.5-77.0%) in patients with good outcome and 71.8% (63.3-74.0%) in patients with poor outcome, p = 0.943. There was no significant association between rSO over time and neurological outcome. In a binary logistic regression model, rSO was not a statistically significant predictor of good neurological outcome (odds ratio 0.99, 95% confidence interval 0.94-1.04, p = 0.635).

Conclusions: We found no association between cerebral oxygenation measured with NIRS and NSE concentrations or outcome in patients resuscitated from OHCA.

Trial Registration: ClinicalTrials.gov, NCT02698917 . Registered on 26 January 2016.
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http://dx.doi.org/10.1186/s13054-019-2428-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518726PMC
May 2019

Usefulness of neuron specific enolase in prognostication after cardiac arrest: Impact of age and time to ROSC.

Resuscitation 2019 06 22;139:214-221. Epub 2019 Apr 22.

Department of Anaesthesiology and Intensive Care, North Karelia Central Hospital, Joensuu, Finland; Department of Anaesthesiology, Kuopio University Hospital, Kuopio, Finland; University of Eastern Finland, Kuopio, Finland.

Aim Of The Study: We evaluated the impact of patient age and time from collapse to return of spontaneous circulation (ROSC) on the prognostic accuracy of neuron specific enolase (NSE) after out-of-hospital cardiac arrest (OHCA).

Methods: Using electrochemiluminescence immunoassay, we measured serum concentrations of NSE in 249 patients who were admitted to intensive care units after resuscitation from OHCA. In each quartile according to age and time to ROSC, we evaluated the ability of NSE at 48 h after OHCA to predict poor outcome (Cerebral Performance Category 3-5) at 12 months.

Results: The outcome at 12 months was poor in 121 (49%) patients. The prognostic performance of NSE was excellent (area under the receiver operating characteristic curve, AUROC, 0.91 [95% confidence interval, 0.81-1.00]) in the youngest quartile (18-56 years), but worsened with increasing age, and was poor (AUROC 0.53 [0.37-0.70]) in the oldest quartile (72 years or more). The prognostic performance of NSE was worthless (AUROC 0.45 [0.30-0.61]) in the quartile with the shortest time to ROSC (1-13 min), but improved with increasing time to ROSC, and was good (AUROC 0.84 [0.74-0.95]) in the quartile with the longest time to ROSC (29 min or over).

Conclusion: NSE at 48 h after OHCA is a useful predictor of 12-month-prognosis in young patients and in patients with a long time from collapse to ROSC, but not in old patients or patients with a short time to ROSC.
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http://dx.doi.org/10.1016/j.resuscitation.2019.04.021DOI Listing
June 2019

Direct Estimation of HDL-Mediated Cholesterol Efflux Capacity from Serum.

Clin Chem 2019 08 17;65(8):1042-1050. Epub 2019 Apr 17.

Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland;

Background: HDL-mediated cholesterol efflux capacity (HDL-CEC) is a functional attribute that may have a protective role in atherogenesis. However, the estimation of HDL-CEC is based on in vitro cell assays that are laborious and hamper large-scale phenotyping.

Methods: Here, we present a cost-effective high-throughput nuclear magnetic resonance (NMR) spectroscopy method to estimate HDL-CEC directly from serum. We applied the new method in a population-based study of 7603 individuals including 574 who developed incident coronary heart disease (CHD) during 15 years of follow-up, making this the largest quantitative study for HDL-CEC.

Results: As estimated by NMR-spectroscopy, a 1-SD higher HDL-CEC was associated with a lower risk of incident CHD (hazards ratio, 0.86; 95%CI, 0.79-0.93, adjusted for traditional risk factors and HDL-C). These findings are consistent with published associations based on in vitro cell assays.

Conclusions: These corroborative large-scale findings provide further support for a potential protective role of HDL-CEC in CHD and substantiate this new method and its future applications.
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http://dx.doi.org/10.1373/clinchem.2018.299222DOI Listing
August 2019

Targeting low-normal or high-normal mean arterial pressure after cardiac arrest and resuscitation: a randomised pilot trial.

Intensive Care Med 2018 Dec 15;44(12):2091-2101. Epub 2018 Nov 15.

Department of Intensive Care, North Karelia Central Hospital, Joensuu, Finland.

Purpose: We aimed to determine the feasibility of targeting low-normal or high-normal mean arterial pressure (MAP) after out-of-hospital cardiac arrest (OHCA) and its effect on markers of neurological injury.

Methods: In the Carbon dioxide, Oxygen and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial, we used a 2 factorial design to randomly assign patients after OHCA and resuscitation to low-normal or high-normal levels of arterial carbon dioxide tension, to normoxia or moderate hyperoxia, and to low-normal or high-normal MAP. In this paper we report the results of the low-normal (65-75 mmHg) vs. high-normal (80-100 mmHg) MAP comparison. The primary outcome was the serum concentration of neuron-specific enolase (NSE) at 48 h after cardiac arrest. The feasibility outcome was the difference in MAP between the groups. Secondary outcomes included S100B protein and cardiac troponin (TnT) concentrations, electroencephalography (EEG) findings, cerebral oxygenation and neurological outcome at 6 months after cardiac arrest.

Results: We recruited 123 patients and included 120 in the final analysis. We found a clear separation in MAP between the groups (p < 0.001). The median (interquartile range) NSE concentration at 48 h was 20.6 µg/L (15.2-34.9 µg/L) in the low-normal MAP group and 22.0 µg/L (13.6-30.9 µg/L) in the high-normal MAP group, p = 0.522. We found no differences in the secondary outcomes.

Conclusions: Targeting a specific range of MAP was feasible during post-resuscitation intensive care. However, the blood pressure level did not affect the NSE concentration at 48 h after cardiac arrest, nor any secondary outcomes.
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http://dx.doi.org/10.1007/s00134-018-5446-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280836PMC
December 2018

Targeting two different levels of both arterial carbon dioxide and arterial oxygen after cardiac arrest and resuscitation: a randomised pilot trial.

Intensive Care Med 2018 Dec 14;44(12):2112-2121. Epub 2018 Nov 14.

Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Purpose: We assessed the effects of targeting low-normal or high-normal arterial carbon dioxide tension (PaCO) and normoxia or moderate hyperoxia after out-of-hospital cardiac arrest (OHCA) on markers of cerebral and cardiac injury.

Methods: Using a 2 factorial design, we randomly assigned 123 patients resuscitated from OHCA to low-normal (4.5-4.7 kPa) or high-normal (5.8-6.0 kPa) PaCO and to normoxia (arterial oxygen tension [PaO] 10-15 kPa) or moderate hyperoxia (PaO 20-25 kPa) and to low-normal or high-normal mean arterial pressure during the first 36 h in the intensive care unit. Here we report the results of the low-normal vs. high-normal PaCO and normoxia vs. moderate hyperoxia comparisons. The primary endpoint was the serum concentration of neuron-specific enolase (NSE) 48 h after cardiac arrest. Secondary endpoints included S100B protein and cardiac troponin concentrations, continuous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) results and neurologic outcome at 6 months.

Results: In total 120 patients were included in the analyses. There was a clear separation in PaCO (p < 0.001) and PaO (p < 0.001) between the groups. The median (interquartile range) NSE concentration at 48 h was 18.8 µg/l (13.9-28.3 µg/l) in the low-normal PaCO group and 22.5 µg/l (14.2-34.9 µg/l) in the high-normal PaCO group, p = 0.400; and 22.3 µg/l (14.8-27.8 µg/l) in the normoxia group and 20.6 µg/l (14.2-34.9 µg/l) in the moderate hyperoxia group, p = 0.594). High-normal PaCO and moderate hyperoxia increased NIRS values. There were no differences in other secondary outcomes.

Conclusions: Both high-normal PaCO and moderate hyperoxia increased NIRS values, but the NSE concentration was unaffected.

Registration: ClinicalTrials.gov, NCT02698917. Registered on January 26, 2016.
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http://dx.doi.org/10.1007/s00134-018-5453-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280824PMC
December 2018

Reaching and grasping with the tongue: Shared motor planning between hand actions and articulatory gestures.

Q J Exp Psychol (Hove) 2018 Oct 1;71(10):2129-2141. Epub 2018 Jan 1.

2 Phonetics and Speech Synthesis Research Group, Department of Modern Languages, University of Helsinki, Helsinki, Finland.

Research has shown connections between articulatory mouth actions and manual actions. This study investigates whether forward-backward hand movements could be associated with vowel production processes that programme tongue fronting/backing, lip rounding/spreading (Experiment 1), and/or consonant production processes that programme tongue tip and tongue dorsum actions (Experiment 2). The participants had to perform either forward or backward hand movement and simultaneously pronounce different vowels or consonants. The results revealed a response benefit, measured in vocal and manual reaction times, when the responses consisted of front vowels and forward hand movements. Conversely, back vowels were associated with backward hand movements. Articulation of rounded versus unrounded vowels or coronal versus dorsal consonants did not produce the effect. In contrast, when the manual responses of forward-backward hand movements were replaced by precision and power grip responses, the coronal consonants [t] and [r] were associated with the precision grip, whereas the dorsal consonant [k] was associated with the power grip. We propose that the movements of the tongue body, operating mainly for vowel production, share the directional action planning processes with the hand movements. Conversely, the tongue articulators related to tongue tip and dorsum movements, operating mainly for consonant production, share the action planning processes with the precision and power grip, respectively.
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http://dx.doi.org/10.1177/1747021817738732DOI Listing
October 2018

Surviving out-of-hospital cardiac arrest: The neurological and functional outcome and health-related quality of life one year later.

Resuscitation 2018 08 15;129:19-23. Epub 2018 May 15.

Division of Intensive Care, Department of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki University Hospital and University of Helsinki, Finland.

Background: Data on long-term functional outcome and quality of life (QoL) after out-of-hospital cardiac arrest (OHCA) are limited. We assessed long-term functional outcome and health-related QoL of OHCA survivors regardless of arrest aetiology.

Methods: All adult unconscious OHCA patients treated in 21 Finnish ICUs between March 2010 and February 2011 were followed. Barthel Index (BI), activities of daily living (ADL), accommodation, help needed and received, working status, car driving and self-experienced cognitive deficits were assessed in 1-year survivors (N = 206, 40.9% of the original FINNRESUSCI cohort) with a structured telephone interview. Health-related QoL and more complex ADL-functions were evaluated by EQ-5D and instrumental ADL questionnaires.

Results: Good outcome, defined as Cerebral Performance Categories 1 or 2, had been reached by 90.3% of survivors. The median BI score was 100, and 91.3% of survivors were independent in basic ADL-functions. The great majority of survivors were living at home, only 8.7% lived in a sheltered home or needed institutionalized care. Of home-living survivors 71.4% scored high in instrumental ADL assessment. The majority (72.6%) of survivors who were working previously had returned to work. Health-related QoL was similar as in age- and gender-adjusted Finnish population.

Conclusions: Long-term functional outcome was good in over 90% of patients surviving OHCA, with health-related quality of life similar to that of an age and gender matched population.
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http://dx.doi.org/10.1016/j.resuscitation.2018.05.011DOI Listing
August 2018

Lower heart rate is associated with good one-year outcome in post-resuscitation patients.

Resuscitation 2018 07 5;128:112-118. Epub 2018 May 5.

Division of Intensive Care, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Optimal hemodynamic goals in post-resuscitation patients are not clear. Previous studies have reported an association between lower heart rate and good outcome in patients receiving targeted temperature management (TTM) after out-of-hospital cardiac arrest.

Methods: We analyzed heart rate (HR) and outcome data of 504 post-resuscitation patients from the prospectively collected database of the FINNRESUSCI study. One-year neurologic outcome was dichotomized by the Cerebral Performance Category (CPC) to good (1-2) or poor (3-5).

Results: Of 504 patients, 40.1% (202/504) had good and 59.9% (302/ 504) had poor one-year neurologic outcome. Patients with good outcome had lower time-weighted mean HR during the first 48 h in the ICU (69.2 bpm [59.2-75.1] vs. 76.6 bpm [65.72-89.6], p < 0.001) and the first 72 h in the ICU (71.2 bpm [65.0-79.0] vs. 77.1 bpm [69.1-90.1, p < 0.001]). The percentage of HR registrations below HR threshold values (60, 80 and 100 bpm) were higher for patients with good neurologic outcome, p < 0.001 for all. Lower time-weighted HR for 0-48 h and 0-72 h, and a higher percentage of HR recordings below threshold values were independently associated with good neurological one-year outcome (p < 0.05 for all). When TTM and non-TTM patients were analyzed separately, HR parameters were independently associated with one-year neurologic outcome only in non-TTM patients.

Conclusion: Lower heart rate was independently associated with good neurologic outcome. Whether HR in post-resuscitation patients is a prognostic indicator or an important variable to be targeted by treatment, needs to be assessed in future prospective controlled clinical trials.
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http://dx.doi.org/10.1016/j.resuscitation.2018.05.001DOI Listing
July 2018

Early Lactate Values After Out-of-Hospital Cardiac Arrest: Associations With One-Year Outcome.

Shock 2019 02;51(2):168-173

Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

Background: Previous studies have shown associations between high admission serum lactate, lower lactate clearance, and increased short-term mortality after out-hospital cardiac arrest (OHCA). We studied whether lactate levels predict long- term outcome after OHCA.

Methods: We included 458 OHCA patients with lactate measurements during intensive care unit (ICU) stay from the prospective FINNRESUSCI study. We evaluated thresholds for time-weighted (TW) mean lactate values for the first 24, 48, and 72 h. We analyzed lactate clearance and used multivariate regression to assess the prognostic value of the different measurement time points.

Results: The admission lactate (median [IQR] 3.06 [2.68-3.44] mmol/L vs 4.76 [4.29-5.23] mmol/L) and the last measured lactate (0.98 [0.90-1.06] mmol/L vs 2.40 [2.03-2.78] mmol/L) were higher in non-survivors than in survivors, as were the lowest (0.73 [0.67-0.79] mmol/L vs 1.83 [1.52-2.14] mmol/L) and the highest (3.44 [3.05-3.83] mmol/L vs 5.25 [4.76-5.74] mmol/L) lactate values (all P < 0.001). Time-weighted mean lactate values for the first 24, 48, 72, and for the entire ICU stay were lower in patients with good outcome (P < 0.001). In multivariate backward regression models, time-weighted mean lactate for the entire ICU stay (OR 1.41 per mmol/L, CI 95% 1.08-1.86, P = 0.013) and the last measured lactate in the ICU (OR 2.16 per mmol/L, CI 95% 1.47-3.18, P < 0.001) were independent predictors of poor 1-year outcome.

Conclusions: In the present study time-weighted mean lactate values for the entire ICU stay, and the last measured lactate value in the ICU, but not admission lactate or lactate clearance were independent predictors of poor 1-year outcome.
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http://dx.doi.org/10.1097/SHK.0000000000001145DOI Listing
February 2019

Procalcitonin and Presepsin as Prognostic Markers After Out-of-Hospital Cardiac Arrest.

Shock 2018 10;50(4):395-400

Division of Intensive Care Medicine, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Patients resuscitated from cardiac arrest commonly develop an inflammatory response called post-cardiac arrest syndrome that clinically resembles septic shock.Procalcitonin and presepsin are associated with inflammation. We hypothesized that these biomarkers reflect the severity of post-cardiac arrest syndrome and predict short-term hemodynamical instability and long-term neurological outcome after cardiac arrest.

Methods: As a subcohort analysis of a prospective, observational, multicenter study "FINNRESUSCI," we obtained plasma from 277 intensive care unit (ICU) patients treated following out-of-hospital cardiac arrest (OHCA). Procalcitonin and presepsin levels were measured 0 to 6 h from ICU admission and 24, 48, and 96 h thereafter. We defined poor outcome as a 12-month Cerebral Performance Category of 3 to 5. We tested statistical associations between biomarkers and hemodynamical parameters and outcome with regression models.

Results: Plasma procalcitonin had best predictive value for 12-month poor outcome at 96 h (AUC 0.76; 95% CI 0.68-0.83) and presepsin at ICU admission (AUC 0.72; 95% CI 0.65-0.78). Elevated procalcitonin concentration at ICU admission predicted unstable hemodynamics in the following 48 h in a linear regression model. In a multivariate logistic regression model with clinical variables, only procalcitonin at 96 h had independent prognostic value for poor 12-month neurological outcome.

Conclusions: Elevated procalcitonin is associated with hemodynamical instability and worsened long-term outcome in OHCA patients. The association is not strong enough for it to be used as a single predictor. Presepsin did not provide clinically relevant information for risk stratification after OHCA.
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http://dx.doi.org/10.1097/SHK.0000000000001087DOI Listing
October 2018