Search

Objective: Wearable nonelectroencephalographic biosignal recordings captured from the wrist offer enormous potential for seizure monitoring. However, signal quality remains a challenging factor affecting data reliability. Models trained for seizure detection depend on the quality of recordings in peri‐ictal periods in performing a feature‐based separation of ictal periods from interictal periods. Thus, this study aims to investigate the effect of epileptic seizures on signal quality, ensuring accurate and reliable monitoring. Methods: This study assesses the signal quality of wearable data during peri‐ictal phases of generalized tonic–clonic and focal to bilateral tonic–clonic seizures (TCS), focal motor seizures (FMS), and focal nonmotor seizures (FNMS). We evaluated accelerometer (ACC) activity and the signal quality of electrodermal activity (EDA) and blood volume pulse (BVP) data. Additionally, we analyzed the influence of peri‐ictal movements as assessed by ACC (ACC activity) on signal quality and examined intraictal subphases of focal to bilateral TCS. Results: We analyzed 386 seizures from 111 individuals in three international epilepsy monitoring units. BVP signal quality and ACC activity levels differed between all seizure types. We found the largest decrease in BVP signal quality and increase in ACC activity when comparing the ictal phase to the pre‐ and postictal phases for TCS. Additionally, ACC activity was strongly negatively correlated with BVP signal quality for TCS and FMS, and weakly for FNMS. Intraictal analysis revealed that tonic and clonic subphases have the lowest BVP signal quality and the highest ACC activity. Significance: Motor elements of seizures significantly impair BVP signal quality, but do not have significant effect on EDA signal quality, as assessed by wrist‐worn wearables. The results underscore the importance of signal quality assessment methods and careful selection of robust modalities to ensure reliable seizure detection. Future research is needed to explain whether seizure detection models' decisions are based on signal responses induced by physiological processes as opposed to artifacts. [ABSTRACT FROM AUTHOR]

Objectives: High counts of averaged interictal epileptiform discharges (IEDs) are key components of accurate interictal electric source imaging (ESI) in patients with focal epilepsy. Automated detections may be time‐efficient, but they need to identify the correct IED types. Thus we compared semiautomated and automated detection of IED types in long‐term video‐EEG (electroencephalography) monitoring (LTM) using an extended scalp EEG array and short‐term high‐density EEG (hdEEG) with visual detection of IED types and the seizure‐onset zone (SOZ). Methods: We prospectively recruited consecutive patients from four epilepsy centers who underwent both LTM with 40‐electrode scalp EEG and short‐term hdEEG with 256 electrodes. Only patients with a single circumscribed SOZ in LTM were included. In LTM and hdEEG, IED types were identified visually, semiautomatically and automatically. Concordances of semiautomated and automated detections in LTM and hdEEG, as well as visual detections in hdEEG, were compared against visually detected IED types and the SOZ in LTM. Results: Fifty‐two of 62 patients with LTM and hdEEG were included. The most frequent IED types per patient, detected semiautomatically and automatically in LTM and visually in hdEEG, were significantly concordant with the most frequently visually identified IED type in LTM and the SOZ. Semiautomated and automated detections of IED types in hdEEG were significantly concordant with visually identified IED types in LTM, only when IED types with more than 50 detected single IEDs were selected. The threshold of 50 detected IED in hdEEG was reached in half of the patients. For all IED types per patient, agreement between visual and semiautomated detections in LTM was high. Significance: Semiautomated and automated detections of IED types in LTM show significant agreement with visually detected IED types and the SOZ. In short‐term hdEEG, semiautomated detections of IED types are concordant with visually detected IED types and the SOZ in LTM if high IED counts were detected. [ABSTRACT FROM AUTHOR]

The Wearables for Epilepsy And Research (WEAR) International Study Group identified a set of methodology standards to guide research on wearable devices for seizure detection. We formed an international consortium of experts from clinical research, engineering, computer science, and data analytics at the beginning of 2020. The study protocols and practical experience acquired during the development of wearable research studies were discussed and analyzed during bi‐weekly virtual meetings to highlight commonalities, strengths, and weaknesses, and to formulate recommendations. Seven major essential components of the experimental design were identified, and recommendations were formulated about: (1) description of study aims, (2) policies and agreements, (3) study population, (4) data collection and technical infrastructure, (5) devices, (6) reporting results, and (7) data sharing. Introducing a framework of methodology standards promotes optimal, accurate, and consistent data collection. It also guarantees that studies are generalizable and comparable, and that results can be replicated, validated, and shared. [ABSTRACT FROM AUTHOR]

Summary: The manageable toxicity profile of obinutuzumab (GA101; G) alone or with chemotherapy in first‐line (1L; fit and non‐fit) and relapsed/refractory (R/R) patients with chronic lymphocytic leukaemia (CLL) was established in the primary analysis of the Phase IIIb GREEN trial (Clinicaltrials.gov: NCT01905943). The final analysis (cut‐off, 31 January 2019) is reported here. Patients received G (1000 mg) alone (G‐mono; fit and non‐fit patients) or with chemotherapy [fludarabine and cyclophosphamide (FC; fit patients); chlorambucil (non‐fit patients); bendamustine (any patient)]. Study endpoints were safety (primary) and efficacy (secondary). Subgroup analyses were performed on prognostic biomarkers in 1L CLL. Overall, 630 patients received 1L and 341 received R/R CLL treatment. At the final analysis, no new safety signals were observed [Grade ≥ 3 adverse events (AEs): 1L 82·7%, R/R 84·5%; serious AEs: 1L 58·1%, R/R 62·5%]. Neutropenia (1L 50·5%, R/R 53·4%) and thrombocytopenia (1L 14·6%, R/R 19·1%) were the most common Grade 3–5 AEs. G‐mono‐, G‐bendamustine and G‐FC‐treated patients with unmutated immunoglobulin heavy chain trended towards shorter progression‐free survival. Achievement of minimal residual disease negativity was greatest in 1L patients treated with G‐FC. In this final analysis of the GREEN trial, the safety profile of G was consistent with current risk management strategies. Biomarker analyses supported efficacy in the specific subgroups. [ABSTRACT FROM AUTHOR]

Noninvasive wearable devices have great potential to aid the management of epilepsy, but these devices must have robust signal quality, and patients must be willing to wear them for long periods of time. Automated machine learning classification of wearable biosensor signals requires quantitative measures of signal quality to automatically reject poor‐quality or corrupt data segments. In this study, commercially available wearable sensors were placed on patients with epilepsy undergoing in‐hospital or in‐home electroencephalographic (EEG) monitoring, and healthy volunteers. Empatica E4 and Biovotion Everion were used to record accelerometry (ACC), photoplethysmography (PPG), and electrodermal activity (EDA). Byteflies Sensor Dots were used to record ACC and PPG, the Activinsights GENEActiv watch to record ACC, and Epitel Epilog to record EEG data. PPG and EDA signals were recorded for multiple days, then epochs of high‐quality, marginal‐quality, or poor‐quality data were visually identified by reviewers, and reviewer annotations were compared to automated signal quality measures. For ACC, the ratio of spectral power from 0.8 to 5 Hz to broadband power was used to separate good‐quality signals from noise. For EDA, the rate of amplitude change and prevalence of sharp peaks significantly differentiated between good‐quality data and noise. Spectral entropy was used to assess PPG and showed significant differences between good‐, marginal‐, and poor‐quality signals. EEG data were evaluated using methods to identify a spectral noise cutoff frequency. Patients were asked to rate the usability and comfort of each device in several categories. Patients showed a significant preference for the wrist‐worn devices, and the Empatica E4 device was preferred most often. Current wearable devices can provide high‐quality data and are acceptable for routine use, but continued development is needed to improve data quality, consistency, and management, as well as acceptability to patients. [ABSTRACT FROM AUTHOR]

Objective: Movement‐based wearable sensors are used for detection of convulsive seizures. The identification of the absence of motion following a seizure, known as post‐ictal immobility (PI), may represent a potential additional application of wearables. PI has been associated with potentially life‐threatening complications and with sudden unexpected death in epilepsy (SUDEP). We aimed to assess whether wearable accelerometers (ACCs) could be used as a digital marker of PI. Method: Devices with embedded ACCs were worn by patients admitted to an epilepsy monitoring unit. Participants presenting with convulsive seizures were included in the study. PI presence and duration were assessed by experts reviewing video recordings. An algorithm for the automatic detection of post‐ictal ACC silence and its duration was developed and the linear pairwise relationship between the automatically detected duration of post‐ictal ACC silence and the duration of the expert‐labeled PI was analyzed. Results: Twenty‐two convulsive seizures were recorded from 18 study participants. Twenty were followed by PI and two by agitation. The automated estimation of post‐ictal ACC silence identified all the 20 expert‐labeled PI. The regression showed that the duration of the post‐ictal ACC silence was correlated with the duration of PI (Pearson r =.92; P <.001), with the age of study participants (Pearson r =.78; P <.001), and with the duration of post‐ictal generalized electroencephalography suppression (PGES; Pearson r =.4; P =.033). Significance: We highlight a novel application of wearables as a way to record post‐ictal manifestations associated with an increased risk of SUDEP. The occurrence of a fatal seizure is unpredictable and the continuous, non‐invasive, long‐term identification of risk factors associated with each individual seizure may assume a great clinical importance. [ABSTRACT FROM AUTHOR]

The article offers information on the chronic lymphocytic leukaemia (CLL) X4 trial which was conducted to harness the anti-CD20 antibody, ofatumumab, for disease-control peri-transplantation and prevention of chronic graft-versus-host disease (GVHD.) Topic discussed diagnosis of patients by flow cytometry of peripheral blood; treatment which comprised of induction therapy and observed that allogeneic Hematopoietic Cell Transplantation (alloHCT) had no significant impact on overall survival.

The article reports on a study which investigated the impact of telomere length on the outcome of allogeneic stem cell transplantation (SCT) for patients with poor risk chronic lymphocytic leukaemia (CLL) based on the German CLL3X trial which included 100 patients. Topics covered include association of telomere length with clinical characteristics, and analysis of telomere length using quantitative polymerase chain reaction.

Objective Despite high rates of long-lasting remissions in patients with chronic lymphocytic leukaemia ( CLL) treated with chemoimmunotherapy, none of the current therapeutic approaches is curative with the exception of allogeneic transplantation. One strategy to extend progression-free survival and long-term survival might be the establishment of consolidation therapies. Methods In this trial, patients with complete or partial second remission after fludarabine-based treatment received consolidation therapy with alemtuzumab. The aim of this phase I/ II trial was to determine the maximal tolerable dose ( MTD) of alemtuzumab consolidation and to evaluate safety and efficacy in patients who responded to second-line fludarabine-based treatment. Thirteen patients in complete ( CR) or partial remission ( PR) received alemtuzumab dose escalation starting with 10 mg intravenously (iv) once weekly for 8 wk and increasing in 10-mg intervals per dose level. Results The main dose-limiting toxicities ( DLTs) were infectious complications, and the MTD was determined at 10 mg. After alemtuzumab consolidation, seven of 13 patients (53%) were in CR, and four of these patients (30.7%) achieved minimal residual disease ( MRD) negativity (<1 × 10E-4). At a median follow-up of 71.5 months, four patients were progression-free, with a median progression-free survival ( PFS) of 28.5 months after the end of second-line treatment. Conclusion The results provide a safe and efficient schedule with weekly intravenous application of 10 mg of alemtuzumab as a consolidation regime in patients with CLL. [ABSTRACT FROM AUTHOR]

Purpose A phase I/ II trial to assess safety and efficacy of the combination bendamustine, rituximab, and lenalidomide ( BRL) in patients with chronic lymphocytic leukemia ( CLL). Patients and Methods Seventeen relapsed or refractory (R/R) and five previously untreated ( FL) CLL patients were enrolled in the trial. In the R/R cohort, four different dose levels of lenalidomide (maximum 15 mg/d) were used. In the FL cohort, lenalidomide was dose escalated from 5 mg/d to 15 mg/d. Bendamustine was used at doses of 50 or 90 mg/m2 for R/R or FL treatment, respectively. 375 mg/m2 Rituximab were used for the first and 500 mg/m2 for subsequent treatment courses. Treatment consisted of up to six courses of 28 d. Results The maximal tolerable dose of lenalidomide was 5 mg/d. The response rate was 47.1% in R/R and 60% in FL patients. Median progression-free survival was 8.0 months. Median overall survival was 22.9 and 12.3 months, respectively, in R/R and FL patients. Grade 3/4 hematological toxicity was observed in 71.4%, and severe infections in 47.6% of patients. Due to high toxicity and low response rate of BRL, the trial was closed prematurely. Conclusion BRL was associated with a high toxicity rate, a high number of treatment interruptions, and a low remission rate. Therefore, BRL cannot be considered an appropriate treatment option for patients with CLL. [ABSTRACT FROM AUTHOR]

Flow cytometric immunophenotyping has become essential for accurate diagnosis, classification, and disease monitoring in hemato-oncology. The EuroFlow Consortium has established a fully standardized 'all-in-one' pipeline consisting of standardized instrument settings, reagent panels, and sample preparation protocols and software for data analysis and disease classification. For its reproducible implementation, parallel development of a quality assurance (QA) program was required. Here, we report on the results of four consecutive annual rounds of the novel external QA EuroFlow program. The novel QA scheme aimed at monitoring the whole flow cytometric analysis process (cytometer setting, sample preparation, acquisition and analysis) by reading the median fluorescence intensities (MedFI) of defined lymphocytes' subsets. Each QA participant applied the predefined reagents' panel on blood cells of local healthy donors. A uniform gating strategy was applied to define lymphocyte subsets and to read MedFI values per marker. The MedFI values were compared with reference data and deviations from reference values were quantified using performance score metrics. In four annual QA rounds, we analyzed 123 blood samples from local healthy donors on 14 different instruments in 11 laboratories from nine European countries. The immunophenotype of defined cellular subsets appeared sufficiently standardized to permit unified (software) data analysis. The coefficient of variation of MedFI for 7 of 11 markers performed repeatedly below 30%, average MedFI in each QA round ranged from 86 to 125% from overall median. Calculation of performance scores was instrumental to pinpoint standardization failures and their causes. Overall, the new EuroFlow QA system for the first time allowed to quantify the technical variation that is introduced in the measurement of fluorescence intensities in a multicentric setting over an extended period of time. EuroFlow QA is a proficiency test specific for laboratories that use standardized EuroFlow protocols. It may be used to complement, but not replace, established proficiency tests. © 2014 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]