„Mild-behavioral-impairment“-Checkliste

Hintergrund: Das Syndrom einer leichten Verhaltensbeeinträchtigung („mild behavioral impairment syndrome“, MBI) ist definiert durch das Auftreten anhaltender neuropsychiatrischer Symptome im Alter. Die Mild-behavioral-impairment-Checkliste (MBI-C) dient der Erfassung von persistierenden neuropsychiatrischen Symptomen, welche die Präsenz des MBI definieren. Ziel: Erarbeitung einer deutschsprachigen Version der MBI-C und Beurteilung der klinischen Anwendbarkeit. Material undMethoden: ImAustausch mit dem federführenden Autor der englischen Originalversionwurde eine deutsche Version erstellt. Die Praktikabilität der Anwendung wurde im Rahmen einer Anwendbarkeitsstudie an einer Kohorte von 21 stationären alterspsychiatrischen Patienten überprüft. Dabei wurden die Compliance der Patienten, die Verständlichkeit, der Zeitaufwand, das Vorgehen bei der Auswertung und die Unterschiede zwischen den Angaben der Patienten und der Angehörigen beurteilt. Ergebnisse: Die erstellte Übersetzung der MBI-C gilt als offizielle deutsche Version und kann auf https://mbitest.org heruntergeladen werden. Alle Patienten beantworteten alle 34 Fragen vollständig, die Verständlichkeit zeigte sich als sehr gut, der durchschnittliche Zeitaufwand lag bei 16min. Es zeigten sich z. T. bedeutsame Unterschiede zwischen den Angaben der Patienten und der Angehörigen. Diskussion: Das MBI kann bei einem Teil der Personen mit neurodegenerativer demenzieller Erkrankung das ansonsten präsymptomatische Stadium markieren. Die MBI-C könnte somit bei der Früherkennung von neurodegenerativen Demenzen helfen. Diese Hypothese kann mithilfe der hier präsentierten sprachlich lokalisierten Version der MBI-C auch im deutschsprachigen Raumzukünftig überprüft werden

Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial

BACKGROUND: Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH. METHODS: We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis. RESULTS: Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P=0.40). There was a signal for interaction with onset-to-treatment time (P$_{interaction}$=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P=0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P=0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation. CONCLUSIONS: In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH

Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial.

BACKGROUND Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH. METHODS We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis. RESULTS Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P=0.40). There was a signal for interaction with onset-to-treatment time (Pinteraction=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P=0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P=0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation. CONCLUSIONS In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH. REGISTRATION URL: https://clinicaltrials.gov; Unique identifier: NCT02866838

Neurons expressing calcium-binding proteins in neocortex of patients with epilepsy and in the perirhinal cortex of the rat

Cortical inhibitory interneurons play an important role in cortical neuronal circuits in physiological state and probably also in the etiopathogenesis of epilepsy. The first part of my research work was focused on calretinin expressing (CR+) interneurons in a) non-malformed temporal neocortex in patients with refractory temporal lobe epilepsy associated with hippocampal sclerosis (nHSTN), b) in focal cortical dysplasias (FCD). FCD represent a prominent cause of pharmacologically intractable epilepsy. Main goal of our study was to show whether CR+ interneurons exhibit any change in human nHSTN and in various types of FCD and to compare it with previously well documented decrease of parvalbumin expressing (PV+) interneurons. We used immunohistochemical staining for CR. Brain tissue from 24 patients surgically treated for pharmacoresistant epilepsy as well as post-mortem acquired control neocortical samples of 9 patients were examined. CR+ interneuronal density in all types of samples was evaluated. In nHSTN, no change compared to controls was found in CR+ neuronal density. The density of CR+ interneurons was significantly decreased in FCD type I (to approximately 70 % of control values) and even more in FCD type II (to approximately 50 % of control values). The decrease of CR+ interneuronal density was shown..

At The Top of the Interneuronal Pyramid - Calretinin Expressing Cortical Interneurons

It is in general well appreciated that the cortical interneurons play various important roles in cortical neuronal networks both in normal and pathological states. Based on connectivity pattern, developmental, morphological and electrophysiological properties, distinct subgroups of GABAergic interneurons can be differentiated in the neocortex as well as in the hippocampal formation. In this E-Book, we are focusing our attention on inhibitory interneurons expressing calcium-binding protein calretinin (CR). The aim of the E-Book is to consolidate the knowledge about this interneuronal population and to inspire further research on the function and malfunction of these neurons, which – functionally – seem to stand "at the top of the pyramid" of cortical interneuronal types

Effectiveness of an Individualized Exergame-Based Motor-Cognitive Training Concept Targeted to Improve Cognitive Functioning in Older Adults With Mild Neurocognitive Disorder: Study Protocol for a Randomized Controlled Trial

Background: Simultaneous motor-cognitive training is considered promising for preventing the decline in cognitive functioning in older adults with mild neurocognitive disorder (mNCD) and can be highly motivating when applied in the form of exergaming. The literature points to opportunities for improvement in the application of exergames in individuals with mNCD by developing novel exergames and exergame-based training concepts that are specifically tailored to patients with mNCD and ensuring the implementation of effective training components. Objective: This study systematically explores the effectiveness of a newly developed exergame-based motor-cognitive training concept (called “Brain-IT”) targeted to improve cognitive functioning in older adults with mNCD. Methods: A 2-arm, parallel-group, single-blinded randomized controlled trial with a 1:1 allocation ratio (ie, intervention: control), including 34 to 40 older adults with mNCD will be conducted between May 2022 and December 2023. The control group will proceed with the usual care provided by the (memory) clinics where the patients are recruited. The intervention group will perform a 12-week training intervention according to the “Brain-IT” training concept, in addition to usual care. Global cognitive functioning will be assessed as the primary outcome. As secondary outcomes, domain-specific cognitive functioning, brain structure and function, spatiotemporal parameters of gait, instrumental activities of daily living, psychosocial factors, and resting cardiac vagal modulation will be assessed. Pre- and postintervention measurements will take place within 2 weeks before starting and after completing the intervention. A 2-way analysis of covariance or the Quade nonparametric analysis of covariance will be computed for all primary and secondary outcomes, with the premeasurement value as a covariate for the predicting group factor and the postmeasurement value as the outcome variable. To determine whether the effects are substantive, partial eta-squared (η2p) effect sizes will be calculated for all primary and secondary outcomes. Results: Upon the initial submission of this study protocol, 13 patients were contacted by the study team. Four patients were included in the study, 2 were excluded because they were not eligible, and 7 were being informed about the study in detail. Of the 4 included patients, 2 already completed all premeasurements and were in week 2 of the intervention period. Data collection is expected to be completed by December 2023. A manuscript of the results will be submitted for publication in a peer-reviewed open-access journal in 2024. Conclusions: This study contributes to the evidence base in the highly relevant area of preventing disability because of cognitive impairment, which has been declared a public health priority by the World Health Organization. Trial Registration: ClinicalTrials.gov NCT05387057; https://clinicaltrials.gov/ct2/show/NCT05387057ISSN:1929-074

Effectiveness of an Individualized Exergame-Based Motor-Cognitive Training Concept Targeted to Improve Cognitive Functioning in Older Adults With Mild Neurocognitive Disorder: Study Protocol for a Randomized Controlled Trial

BACKGROUND Simultaneous motor-cognitive training is considered promising for preventing the decline in cognitive functioning in older adults with mild neurocognitive disorder (mNCD) and can be highly motivating when applied in the form of exergaming. The literature points to opportunities for improvement in the application of exergames in individuals with mNCD by developing novel exergames and exergame-based training concepts that are specifically tailored to patients with mNCD and ensuring the implementation of effective training components. OBJECTIVE This study systematically explores the effectiveness of a newly developed exergame-based motor-cognitive training concept (called "Brain-IT") targeted to improve cognitive functioning in older adults with mNCD. METHODS A 2-arm, parallel-group, single-blinded randomized controlled trial with a 1:1 allocation ratio (ie, intervention: control), including 34 to 40 older adults with mNCD will be conducted between May 2022 and December 2023. The control group will proceed with the usual care provided by the (memory) clinics where the patients are recruited. The intervention group will perform a 12-week training intervention according to the "Brain-IT" training concept, in addition to usual care. Global cognitive functioning will be assessed as the primary outcome. As secondary outcomes, domain-specific cognitive functioning, brain structure and function, spatiotemporal parameters of gait, instrumental activities of daily living, psychosocial factors, and resting cardiac vagal modulation will be assessed. Pre- and postintervention measurements will take place within 2 weeks before starting and after completing the intervention. A 2-way analysis of covariance or the Quade nonparametric analysis of covariance will be computed for all primary and secondary outcomes, with the premeasurement value as a covariate for the predicting group factor and the postmeasurement value as the outcome variable. To determine whether the effects are substantive, partial eta-squared (η$^{2}$$_{p}$) effect sizes will be calculated for all primary and secondary outcomes. RESULTS Upon the initial submission of this study protocol, 13 patients were contacted by the study team. Four patients were included in the study, 2 were excluded because they were not eligible, and 7 were being informed about the study in detail. Of the 4 included patients, 2 already completed all premeasurements and were in week 2 of the intervention period. Data collection is expected to be completed by December 2023. A manuscript of the results will be submitted for publication in a peer-reviewed open-access journal in 2024. CONCLUSIONS This study contributes to the evidence base in the highly relevant area of preventing disability because of cognitive impairment, which has been declared a public health priority by the World Health Organization. TRIAL REGISTRATION ClinicalTrials.gov NCT05387057; https://clinicaltrials.gov/ct2/show/NCT05387057. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/41173

Influence of Erythropoiesis-Stimulating Agents on HbA1c and Fructosamine in Patients with Haemodialysis

Introduction HbA1c is the most accepted laboratory parameter for the long term observation of glucose control. There is still much of a debate about the use of HbA1c as a metabolic indicator in diabetic patients (DM) on haemodialysis (HD) and erythropoiesis-stimulating agent (ESA) therapy because of the altered erythrocyte turn over in patients with chronic kidney disease and haemodialysis (CKD5D). Patients and Methods In 102 CKD5 patients with and without diabetes mellitus, we examined the dose dependent variability in HbA1c and fructosamine levels under haemodialysis and treated with epoetin a (n = 48) and a new generation agent with continuous stimulation of methoxy polyethylene glycol epoetin beta (C.E.R.A.; n = 54). Results HbA1c levels were affected by therapy with ESA treatments. ESA dose was inversely correlated with HbA1c and an escalation of 10.000 IU per week induced an estimated decrease of HbA1c of 0.6 percent. In addition, the increase of reticulocyte number as a marker for erythropoiesis was significantly inversely correlated with the increase of Delta HbA1c. ESA treatments had no such effect on the alternative metabolic parameter fructosamine. When compared, both therapeutic agents had comparable success in attaining haemoglobin (Hb) target values. C.E.R.A. showed better correlation and was more effective over a longer dose interval. Conclusions Our results show that HbA1c levels in patients should be carefully interpreted based on interfering factors. Nevertheless, HbA1c is currently the most consistent parameter for use ascertaining metabolic status of patients suffering from diabetes mellitus

Dual RAAS Blockade with Aliskiren in Patients with Severely Impaired Chronic Kidney Disease

Abstract Dual renin-angiotensin-aldosterone blockade (dRAASb) is purposed in the prevention of the cardiorenal syndrome (CRS). However, all attempts with dRAASb even in patients with moderate impaired chronic kidney disease (CKD) were terminated due to the typical severe adverse events (SAE), e. g., hyperkalemia and rise of serum creatinine. The aim of our study with the direct renin inhibitor aliskiren was to evaluate the effect of dRAASb with a washout phase in patients with severely advanced CKD. We have studied 45 patients (G3b to 4, A2 and &gt;A3; median glomerular filtration rate (GFR) CKD-EPI 31 (23–40) ml/min per 1.73 m² BSA (body surface area), albumin-creatinine-ratio in urine (UACR) (0.413 (0.164 to 1.39) g/g) and proteinuria (0.5 (0.2 to 0.9) g/l) before, with and without aliskiren (150 respectively 300 mg per day) added to an angiotensin-converting enzyme inhibitor (ACEi) or an AT1-receptor blocker (ARB) over 4 ½ years. The dRAASb with aliskiren showed a significant decrease of proteinuria (0.5 to 0.38 g/l), especially in patients with an UACR≥350 mg/g and in the subgroup analysis e. g., in patients with diabetes, but proteinuria increased in the washout phase again. The blood pressure (130/80 mm Hg), serum potassium (4.9 to 5.0 mmol/l) and GFR remained nearly constant (31 to 29.5 ml/min per 1.73 m2 BSA). A more than 30% increase in serum creatinine was associated with an UACR&gt;300 mg/g. The dRAASb has beneficial effects on proteinuria and is safe in patients with severely advanced CKD. However, in patients with high UACR (&gt;300 mg/g) raise of creatinine and potassium have to be controlled.</jats:p