Summary Background Haematoma expansion is a major cause of mortality in intracranial haemorrhage related to vitamin K antagonists (VKA-ICH). Normalisation of the international normalised ratio (INR) ...is recommended, but optimum haemostatic management is controversial. We assessed the safety and efficacy of fresh frozen plasma (FFP) versus prothrombin complex concentrate (PCC) in patients with VKA-ICH. Methods We did an investigator-initiated, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Patients aged at least 18 years with VKA-ICH who presented within 12 h after symptom onset with an INR of at least 2·0 were randomly assigned (1:1) by numbered sealed envelopes to 20 mL/kg of intravenous FFP or 30 IU/kg of intravenous four-factor PCC within 1 h after initial cerebral CT scan. The primary endpoint was the proportion of patients with INR 1·2 or lower within 3 h of treatment initiation. Masking of treatment was not possible, but the primary analysis was observer masked. Analyses were done using a treated-as-randomised approach. This trial is registered with EudraCT, number 2008-005653-37, and ClinicalTrials.gov , number NCT00928915. Findings Between Aug 7, 2009, and Jan 9, 2015, 54 patients were randomly assigned (26 to FFP and 28 to PCC) and 50 received study drug (23 FFP and 27 PCC). The trial was terminated on Feb 6, 2015, after inclusion of 50 patients after a safety analysis because of safety concerns. Two (9%) of 23 patients in the FFP group versus 18 (67%) of 27 in the PCC group reached the primary endpoint (adjusted odds ratio 30·6, 95% CI 4·7–197·9; p=0·0003). 13 patients died: eight (35%) of 23 in the FFP group (five from haematoma expansion, all occurring within 48 h after symptom onset) and five (19%) of 27 in the PCC group (none from haematoma expansion), the first of which occurred on day 5 after start of treatment. Three thromboembolic events occurred within 3 days (one in the FFP group and two in the PCC group), and six after day 12 (one and five). 43 serious adverse events (20 in the FFP group and 23 in the PCC group) occurred in 26 patients. Six serious adverse events were judged to be FFP related (four cases of haematoma expansion, one anaphylactic reaction, and one ischaemic stroke) and two PCC related (ischaemic stroke and pulmonary embolism). Interpretation In patients with VKA-related intracranial hemorrhage, four-factor PCC might be superior to FFP with respect to normalising the INR, and faster INR normalisation seemed to be associated with smaller haematoma expansion. Although an effect of PCC on clinical outcomes remains to be shown, our data favour the use of PCC over FFP in intracranial haemorrhage related to VKA. Funding Octapharma.
Numerous preclinical findings and a clinical pilot study suggest that recombinant human erythropoietin (EPO) provides neuroprotection that may be beneficial for the treatment of patients with ...ischemic stroke. Although EPO has been considered to be a safe and well-tolerated drug over 2 decades, recent studies have identified increased thromboembolic complications and/or mortality risks on EPO administration to patients with cancer or chronic kidney disease. Accordingly, the double-blind, placebo-controlled, randomized German Multicenter EPO Stroke Trial (Phase II/III; ClinicalTrials.gov Identifier: NCT00604630) was designed to evaluate efficacy and safety of EPO in stroke.
This clinical trial enrolled 522 patients with acute ischemic stroke in the middle cerebral artery territory (intent-to-treat population) with 460 patients treated as planned (per-protocol population). Within 6 hours of symptom onset, at 24 and 48 hours, EPO was infused intravenously (40,000 IU each). Systemic thrombolysis with recombinant tissue plasminogen activator was allowed and stratified for.
Unexpectedly, a very high number of patients received recombinant tissue plasminogen activator (63.4%). On analysis of total intent-to-treat and per-protocol populations, neither primary outcome Barthel Index on Day 90 (P=0.45) nor any of the other outcome parameters showed favorable effects of EPO. There was an overall death rate of 16.4% (n=42 of 256) in the EPO and 9.0% (n=24 of 266) in the placebo group (OR, 1.98; 95% CI, 1.16 to 3.38; P=0.01) without any particular mechanism of death unexpected after stroke.
Based on analysis of total intent-to-treat and per-protocol populations only, this is a negative trial that also raises safety concerns, particularly in patients receiving systemic thrombolysis.
•Air pollution from traffic poses higher risk of stroke than from industrial sources.•No association found between exposure to air pollution and risk of CHD.•Among PM components NH4 and SO4 have ...higher effect on cardiovascular health.
Few studies have examined the risk of long-term exposure to source-specific airborne pollutants on incidence of cerebrovascular and cardiovascular events.
We aimed to estimate the effect of long-term exposure to source-specific air pollution and particulate matter (PM) components on incidence of stroke, coronary heart disease (CHD), and total cardiovascular events (CVE) in the population-based Heinz Nixdorf Recall study (HNR).
We used baseline (2000–2003) and 14-year follow-up data of the HNR Study, an ongoing population-based prospective cohort study in Western Germany. Participants’ residential mean exposures to NO2 and total and source-specific PM10, PM2.5, accumulation mode particle number concentration (PNAM), and PM components were modelled using a dispersion and chemical transport model. We used Cox regression to evaluate the effect of pollutants (per 1 μg/m3 increase and per interquartile range – IQR) on risk of stroke and CHD, adjusting for socio-demographic characteristics, lifestyle risk factors and nighttime traffic noise exposure.
In 4,105 included participants (aged 45–76 at baseline, 52.5% women), we observed 118 cases of first stroke and 373 cases of first CHD during 46,748 person-years under risk. The median survival time within the cohort was 13.3 years. No effect of exposure to ambient air pollution on risk of CHD was observed, but distinct effects were observed for stroke. Ambient traffic-specific PM showed a stronger effect on stroke than industry-specific PM: hazard ratios (95% confidence interval) for total, traffic-specific, and industry-specific PM2.5 were 1.16 (1.02–1.34), 2.53 (1.07–5.97), and 1.27 (1.03–1.56) per 1 μg/m3 increase, respectively. PM components showed no substantially different effects from those of total PM per IQR, but higher associations were observed for NH4 and SO4 per 1 μg/m3. However, the exposure contrast of ammonium and sulfate components was very low.
Traffic-specific PM exhibited stronger effects than total and industry-specific PM on risk of stroke. Among components, NH4 and SO4 showed higher effects. No effect was observed for PM and CHD.
The frequent use of a longer time window for recanalization therapy in patients with basilar artery occlusion (BAO) in daily practice is not supported by any scientific evidence. We investigated the ...relationship between time to recanalization therapy and functional outcome in BAO with data from the Basilar Artery International Cooperation Study (BASICS).
BASICS is a prospective multicenter registry of patients (n=619) with radiologically confirmed BAO. We analyzed patients receiving intravenous thrombolysis or intra-arterial treatment. Patients were divided into 4 groups based on the interval between estimated time of BAO and start of recanalization therapy: ≤3 hours (n=134), >3 to ≤6 hours (n=151), >6 to ≤9 hours (n=56), and >9 hours (n=68). Primary outcome measure was poor functional outcome (modified Rankin scale score 4-6) after 1 month. We calculated adjusted risk ratios with 95% CIs using Poisson regression analyses with the ≤3 hours group as the reference group.
Patients had an increased risk of poor functional outcome as time to recanalization therapy became longer (≤3 hours: 62%; >3 to ≤6 hours: 67% adjusted risk ratio, 1.06; 0.91-1.25; >6 to ≤9 hours: 77% adjusted risk ratio, 1.26; 1.06-1.51; >9 hours: 85% adjusted risk ratio, 1.47; 1.26-1.72).
Early recanalization therapy in patients with BAO is associated with a more favorable outcome with a significant increased chance of a poor outcome when recanalization therapy is started >6 hours after estimated time of BAO.
Abstract
Objective
We provide normative data for the Trail Making Test (TMT)-A and B and the derived scores B − A and B/A, for the German general population aged 57–84 years.
Methods
Data were ...derived from the third examination of the population-based Heinz Nixdorf Recall study. We excluded participants with a history of dementia or stroke, a depression score above cutoff (CES-D Center for Epidemiologic Studies Depression Scale score ≥ 18), or mild cognitive impairment according to a neurocognitive test battery. The normative sample (n = 2,182) was stratified by age, using the interval superposition approach, and by three levels of educational attainment (up to 10 years of schooling; >10 years of schooling; and university degree).
Results
We tabulated test performance scores at percentage rank thresholds 5, 10, 15, 20, 25, 50, 75, and 90. In multiple linear regression, TMT-A performance declined by 1 s each year of life, and TMT-B performance by 3 s; educational level had an impact of up to 30 s in TMT-B. TMT-B/A was only weakly associated with age and education. TMT-B and B − A correlated r = 0.96. Completion of the TMT-B within the time limit of 300 s was not achieved by 10.9% of participants >74 years, and especially by those >74 years who were on the lowest educational level (13.9%).
Conclusions
For TMT-A, TMT-B, and B − A, the narrow age categorization and distinction between three educational levels proved meaningful. The 300 s limit for the TMT-B impedes the identification of thresholds for very low performance in this age group and needs reconsideration.
Detection and diagnosis of early and subclinical stages of Alzheimer's Disease (AD) play an essential role in the implementation of intervention and prevention strategies. Neuroimaging techniques ...predominantly provide insight into anatomic structure changes associated with AD. Deep learning methods have been extensively applied towards creating and evaluating models capable of differentiating between cognitively unimpaired, patients with Mild Cognitive Impairment (MCI) and AD dementia. Several published approaches apply information fusion techniques, providing ways of combining several input sources in the medical domain, which contributes to knowledge of broader and enriched quality. The aim of this paper is to fuse sociodemographic data such as age, marital status, education and gender, and genetic data (presence of an apolipoprotein E (APOE)-ε4 allele) with Magnetic Resonance Imaging (MRI) scans. This enables enriched multi-modal features, that adequately represent the MRI scan visually and is adopted for creating and modeling classification systems capable of detecting amnestic MCI (aMCI). To fully utilize the potential of deep convolutional neural networks, two extra color layers denoting contrast intensified and blurred image adaptations are virtually augmented to each MRI scan, completing the Red-Green-Blue (RGB) color channels. Deep convolutional activation features (DeCAF) are extracted from the average pooling layer of the deep learning system Inception_v3. These features from the fused MRI scans are used as visual representation for the Long Short-Term Memory (LSTM) based Recurrent Neural Network (RNN) classification model. The proposed approach is evaluated on a sub-study containing 120 participants (aMCI = 61 and cognitively unimpaired = 59) of the Heinz Nixdorf Recall (HNR) Study with a baseline model accuracy of 76%. Further evaluation was conducted on the ADNI Phase 1 dataset with 624 participants (aMCI = 397 and cognitively unimpaired = 227) with a baseline model accuracy of 66.27%. Experimental results show that the proposed approach achieves 90% accuracy and 0.90 F1-Score at classification of aMCI vs. cognitively unimpaired participants on the HNR Study dataset, and 77% accuracy and 0.83 F1-Score on the ADNI dataset.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Intracranial hemorrhage (ICH) is a rare but serious side effect associated with the use of oral anticoagulants, such as dabigatran. The specific reversal agent for dabigatran, idarucizumab, is ...available for the management of individuals with ICH. The aim of this study was to provide real-world evidence on patients with ICH and effective treatment with dabigatran and reversal with idarucizumab in clinical routine compared to those under effective treatment with vitamin-K-antagonist (VKA).
Registration of Idarucizumab for Patients with IntraCranial Hemorrhage (RIC-ICH) is a non-interventional study conducted in 22 German stroke units that prospectively enrolled dabigatran patients treated with idarucizumab. Retrospective data from VKA patients served as reference population. Main objective was in-hospital mortality. Further objectives included change in bleeding volume, stroke severity, and functional status.
In-hospital mortality was 26.7% in 15 dabigatran and 27.3% in 88 VKA patients (hazard ratio 1.00, 95% CI 0.29-2.60). In patients with bleeding volume > 60 ml, mortality was lower in the dabigatran group (
= 6, 33%) compared to the VKA group (N = 15, 67%; HR 0.24, 95% CI 0.04-0.96). No differences were observed in secondary endpoints between dabigatran and VKA patients.
These results, based on data from routine clinical practice, suggest that in-hospital mortality after idarucizumab treatment is comparable to that in patients pretreated with VKA. Due to the low precision of estimates, the results must be interpreted with caution.
Background
Depression might be an independent risk factor for cognitive decline, a prodromal dementia symptom or a reaction to cognitive/functional impairment.
Objective
To investigate the ...association between (1) depressive symptoms and (2) depressive symptom patterns over 13 years with incident mild cognitive impairment (MCI) 5 years later.
Materials and methods
We included 724/823 cognitively unimpaired men/women who participated in the population-based Heinz Nixdorf Recall study (t1: 2005–2008, ø62.9 years; t2: 2010–2015, ø68.1 years). Depressive symptoms were assessed in the study center and during six postal follow-ups using the short form of the Center for Epidemiologic Studies Depression Scale (CES-D). Relative risks (RR; 95% confidence intervals) for MCI at t2 (men/women: 71/76) were estimated for CES-D at t1 (linear and dichotomized at ≥17, cut-off for clinically relevant depressive symptoms) and CES-D fluctuations over 13 years (stable low, large fluctuations, stable high/stable around cut-off) using log-linear regression models with Poisson working likelihood adjusted for age, sex, education, diabetes mellitus, coronary heart disease, and stroke.
Results
Fully adjusted risk for MCI at t2 (per CES-D point increase at t1) was elevated for the total cohort (1.053, 1.031–1.076), men (1.046, 1.012–1.081), and women (1.059, 1.029–1.090). Applying the dichotomized CES-D, risk for MCI was substantially increased for the total cohort 2.22 (1.38–3.58) and in women 2.59 (1.46–4.58). Large CES-D fluctuations and stable high/stable around cut-off were associated with increased RR for MCI in the total cohort and in women compared to stable low symptoms.
Conclusion
Depressive symptoms predicted MCI in cognitively unimpaired participants of our population-based study. Adequate treatment of depression may therefore contribute to the maintenance of normal cognition and delay dementia onset.
Mechanical thrombectomy (MT) is a new evidence-based treatment option for large vessel occlusion in the anterior brain circulation. Using comprehensive administrative data from Germany, we analysed ...the nationwide development of intravenous thrombolysis (IVT) and MT in Germany between 2010 and 2016.
We considered all documented cases (
= 1,515,634) with a main diagnosis of the ICD-10-GM code I63 (ischemic stroke) and identified specific stroke recanalization therapy by using the corresponding Operating and Procedure Key for systemic thrombolysis and mechanical thrombectomy out of the DRG statistics. Regional analyses are based on data from the 413 German administrative districts and cities and the obligatory quality reports of all hospitals. We distinguished between rates of MT related to place of residence of patients and place of treatment.
Coded ischemic strokes increased by 10.2% from 2010 (
= 206.688) to 2016 (
= 227.687). The rate of IVT increased from 8.9% in 2010 to 14.9% in 2016 and the rate of MT increased from 0.8% in 2010 to 4.7% in 2016 with a strong increase in 2015 and 2016. There was a high regional variability of MT according to place of residence of patients between 0 and 11.2% in 2016 with significant lower treatment rates in rural compared to urban areas (3.8 vs 5.4%). Mean age of patients treated with MT increased from 67.8 years in 2010 to 73.3 years in 2016 and almost reached the mean age of IVT treated patients (74.4 years). The number of hospitals coding MT increased from 91 to 193 from 2010 to 2016, but 80% of all MT procedures were performed in neurointerventional centers with ≥50 procedures/year in 2016.
The rate of IVT in patients with acute ischemic stroke in Germany continues to rise and has reached 14.9% nationwide. The increase of MT is even more pronounced and was triggered by the evidence after publication of the MT randomized trials. There is still a high regional variability with significant lower MT rates in rural areas.
Abstract
The heterozygous human Klotho KL-VS haplotype has been associated with improved cognitive performance but results are inconsistent. Here we assessed Klotho KL-VS haplotype and cognition ...using data from the third examination of the population-based Heinz Nixdorf Recall Study. We analyzed cognition tests (immediate and delayed word list, Trail-Making Test TMT part A and B, Maze test, interference condition of the Stroop color-word test, verbal fluency) and their associations with Klotho KL-VS haplotype. The Klotho KL-VS haplotype is classified by the V-allele at SNP rs9536314 (F352V) and the S-allele at SNP rs9527025 (C370S). Heterozygotes for the KL-VS haplotype were compared with non-carriers. Analyses were performed in 1812 subjects (55–87 years). We found consistent but only slightly lower performance in heterozygous carriers of the KL-VS haplotype in all tasks with Z-scores ranging between Z = − 0.042 (verbal fluency) and − 0.17 (TMT part A). Differences between carriers and non-carriers were similar for men and women for all tests but TMT part B (interaction contrast = 8.4 s (95% CI − 2.3; 19.1)). While cognition declined with age, we found an effect modification by age (55–65 years, 66–75 years, > 75 years). In the 66–75 years KL-VS heterozygous age group, lower performance was seen in memory, visual attention and motor speed. Contrary to our hypothesis, heterozygous carriers of the KL-VS haplotype did not show enhanced performance in cognitive tests in our study.
PDF
