Publications by authors named "Torsten Rackoll"

5 Publications

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Applying time series analyses on continuous accelerometry data-A clinical example in older adults with and without cognitive impairment.

PLoS One 2021 13;16(5):e0251544. Epub 2021 May 13.

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Research Berlin (CSB), Berlin, Germany.

Introduction: Many clinical studies reporting accelerometry data use sum score measures such as percentage of time spent in moderate to vigorous activity which do not provide insight into differences in activity patterns over 24 hours, and thus do not adequately depict circadian activity patterns. Here, we present an improved functional data analysis approach to model activity patterns and circadian rhythms from accelerometer data. As a use case, we demonstrated its application in patients with mild cognitive impairment (MCI) and age-matched healthy older volunteers (HOV).

Methods: Data of two studies were pooled for this analysis. Following baseline cognitive assessment participants were provided with accelerometers for seven consecutive days. A function on scalar regression (FoSR) approach was used to analyze 24 hours accelerometer data.

Results: Information on 48 HOV (mean age 65 SD 6 years) and 18 patients with MCI (mean age 70, SD 8 years) were available for this analysis. MCI patients displayed slightly lower activity in the morning hours (minimum relative activity at 6:05 am: -41.3%, 95% CI -64.7 to -2.5%, p = 0.031) and in the evening (minimum relative activity at 21:40 am: -48.4%, 95% CI -68.5 to 15.4%, p = 0.001) as compared to HOV after adjusting for age and sex.

Discussion: Using a novel approach of FoSR, we found timeframes with lower activity levels in MCI patients compared to HOV which were not evident if sum scores of amount of activity were used, possibly indicating that changes in circadian rhythmicity in neurodegenerative disease are detectable using easy-to-administer accelerometry.

Clinical Trials: Effects of Brain Stimulation During Nocturnal Sleep on Memory Consolidation in Patients With Mild Cognitive Impairments, identifier: NCT01782391. Effects of Brain Stimulation During a Daytime Nap on Memory Consolidation in Patients With Mild Cognitive Impairment, identifier: NCT01782365.
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May 2021

Magnetic resonance imaging-based changes in vascular morphology and cerebral perfusion in subacute ischemic stroke.

J Cereb Blood Flow Metab 2021 Apr 17:271678X211010071. Epub 2021 Apr 17.

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Stroke Research Berlin, Berlin, Germany.

MRI-based vessel size imaging (VSI) allows for assessment of cerebral microvasculature and perfusion. This exploratory analysis of vessel size (VS) and density (Q; both assessed via VSI) in the subacute phase of ischemic stroke involved sixty-two patients from the BAPTISe cohort ('Biomarkers And Perfusion--Training-Induced changes after Stroke') nested within a randomized controlled trial (intervention: 4-week training relaxation). Relative VS, Q, cerebral blood volume (rCBV) and -flow (rCBF) were calculated for: ischemic lesion, perilesional tissue, and region corresponding to ischemic lesion on the contralateral side (mirrored lesion). Linear mixed-models detected significantly increased rVS and decreased rQ within the ischemic lesion compared to the mirrored lesion (coefficient[standard error]: 0.2[0.08] p = 0.03 and -1.0[0.3] p = 0.02, respectively); lesion rCBF and rCBV were also significantly reduced. Mixed-models did not identify time-to-MRI, nor training as modifying factors in terms of rVS or rQ up to two months post-stroke. Larger lesion VS was associated with larger lesion volumes (β 34, 95%CI 6.2-62; p = 0.02) and higher baseline NIHSS (β 3.0, 95%CI 0.49-5.3;p = 0.02), but was not predictive of six-month outcome. In summary, VSI can assess the cerebral microvasculature and tissue perfusion in the subacute phases of ischemic stroke, and may carry relevant prognostic value in terms of lesion volume and stroke severity.
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April 2021

Physical Fitness Training in Patients with Subacute Stroke (PHYS-STROKE): Safety analyses of a randomized clinical trial.

Int J Stroke 2021 Apr 7:17474930211006286. Epub 2021 Apr 7.

Center for Stroke Research Berlin (CSB), Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background And Aim: To report the six-month safety analyses among patients enrolled in the "Physical Fitness Training in Subacute Stroke-PHYS-STROKE" trial and identify underlying risk factors associated with serious adverse events.

Methods: We performed a pre-specified safety analysis of a multicenter, randomized controlled, endpoint-blinded trial comprising 200 patients with moderate to severe subacute stroke (days 5-45 after stroke) that were randomly assigned (1:1) to receive either aerobic, bodyweight supported, treadmill-based training (n = 105), or relaxation sessions (n = 95, control group). Each intervention session lasted for 25 min, five times weekly for four weeks, in addition to standard rehabilitation therapy. Serious adverse events defined as cerebro- and cardiovascular events, readmission to hospital, and death were assessed during six months of follow-up. Incident rate ratios (IRR) were calculated, and Poisson regression analyses were conducted to identify risk factors for serious adverse events and to test the association with aerobic training.

Results: Six months after stroke, 50 serious adverse events occurred in the trial with a higher incidence rate (per 100 patient-months) in the training group compared to the relaxation group (6.31 vs. 3.22; IRR 1.70, 95% CI 0.96 to 3.12). The association of aerobic training with serious adverse events incidence rates were modified by diabetes mellitus (IRR for interaction: 7.10, 95% CI 1.56 to 51.24) and by atrial fibrillation (IRR for interaction: 4.37, 95% CI 0.97 to 31.81).

Conclusions: Safety analysis of the PHYS-STROKE trial found a higher rate of serious adverse events in patients randomized to aerobic training compared to control within six months after stroke. Exploratory analyses found an association between serious adverse events occurrence in the aerobic training group with pre-existing diabetes mellitus and atrial fibrillation which should be further investigated in future trials.

Data Access Statement: The raw data and analyses scripts are provided by the authors on a secure online repository for reproduction of reported findings.
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April 2021

Blinding in electric current stimulation in subacute neglect patients with current densities of 0.8 A/m: a cross-over pilot study.

BMC Res Notes 2021 Jan 25;14(1):35. Epub 2021 Jan 25.

QUEST Center for Transforming Biomedical Research, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Objective: Neglect after stroke is a disabling disorder and its rehabilitation is a major challenge. Transcranial direct current stimulation (tDCS) seems to be a promising adjuvant technique to improve standard care neglect therapy. Since electric fields are influenced by age-related factors, higher current densities are probably needed for effective treatment in aged stroke patients. Validation of treatment efficacy requires sham-controlled experiments, but increased current densities might comprise blinding. Therefore, a pilot study was conducted to test sham adequacy when using current density of 0.8 A/m. Whether especially neglect patients who mainly suffer from perceptual and attentional deficits are able to differentiate beyond chance active from sham tDCS was investigated in a randomized cross-over design (active/sham stimulation) in 12 early subacute patients with left-sided hemineglect. Stimulation (0.8 A/m) was performed simultaneous to standard care neglect therapy.

Results: Odds ratio of correct guessing an atDCS condition compared to wrongly judge an atDCS condition as sham was 10.00 (95%CI 0.65-154.40, p = 0.099). However, given the small sample size and high OR, although likely somewhat overestimated, results require careful interpretation and blinding success in neglect studies with current densities of 0.8 A/m should be further confirmed.
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January 2021

Physical Fitness Training in Patients with Subacute Stroke (PHYS-STROKE): multicentre, randomised controlled, endpoint blinded trial.

BMJ 2019 09 18;366:l5101. Epub 2019 Sep 18.

Centre for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany

Objective: To determine the safety and efficacy of aerobic exercise on activities of daily living in the subacute phase after stroke.

Design: Multicentre, randomised controlled, endpoint blinded trial.

Setting: Seven inpatient rehabilitation sites in Germany (2013-17).

Participants: 200 adults with subacute stroke (days 5-45 after stroke) with a median National Institutes of Health stroke scale (NIHSS, range 0-42 points, higher values indicating more severe strokes) score of 8 (interquartile range 5-12) were randomly assigned (1:1) to aerobic physical fitness training (n=105) or relaxation sessions (n=95, control group) in addition to standard care.

Intervention: Participants received either aerobic, bodyweight supported, treadmill based physical fitness training or relaxation sessions, each for 25 minutes, five times weekly for four weeks, in addition to standard rehabilitation therapy. Investigators and endpoint assessors were masked to treatment assignment.

Main Outcome Measures: The primary outcomes were change in maximal walking speed (m/s) in the 10 m walking test and change in Barthel index scores (range 0-100 points, higher scores indicating less disability) three months after stroke compared with baseline. Safety outcomes were recurrent cardiovascular events, including stroke, hospital readmissions, and death within three months after stroke. Efficacy was tested with analysis of covariance for each primary outcome in the full analysis set. Multiple imputation was used to account for missing values.

Results: Compared with relaxation, aerobic physical fitness training did not result in a significantly higher mean change in maximal walking speed (adjusted treatment effect 0.1 m/s (95% confidence interval 0.0 to 0.2 m/s), P=0.23) or mean change in Barthel index score (0 (-5 to 5), P=0.99) at three months after stroke. A higher rate of serious adverse events was observed in the aerobic group compared with relaxation group (incidence rate ratio 1.81, 95% confidence interval 0.97 to 3.36).

Conclusions: Among moderately to severely affected adults with subacute stroke, aerobic bodyweight supported, treadmill based physical fitness training was not superior to relaxation sessions for maximal walking speed and Barthel index score but did suggest higher rates of adverse events. These results do not appear to support the use of aerobic bodyweight supported fitness training in people with subacute stroke to improve activities of daily living or maximal walking speed and should be considered in future guidelines.

Trial Registration: NCT01953549.
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September 2019