Background and Objectives The choroid plexus has been shown to play a crucial role in CNS inflammation. Previous studies found larger choroid plexus in multiple sclerosis (MS) compared with healthy controls. However, it is not clear whether the choroid plexus is similarly involved in MS and in neuromyelitis optica spectrum disorder (NMOSD). Thus, the aim of this study was to compare the choroid plexus volume in MS and NMOSD. Methods In this retrospective, cross-sectional study, patients were included by convenience sampling from 4 international MS centers. The choroid plexus of the lateral ventricles was segmented fully automatically on T1-weighted MRI sequences using a deep learning algorithm (Multi-Dimensional Gated Recurrent Units). Uni- and multivariable linear models were applied to investigate associations between the choroid plexus volume, clinically meaningful disease characteristics, and MRI parameters. Results We studied 180 patients with MS and 98 patients with NMOSD. In total, 94 healthy individuals and 47 patients with migraine served as controls. The choroid plexus volume was larger in MS (median 1,690 µL, interquartile range [IQR] 648 µL) than in NMOSD (median 1,403 µL, IQR 510 µL), healthy individuals (median 1,533 µL, IQR 570 µL), and patients with migraine (median 1,404 µL, IQR 524 µL; all p < 0.001), whereas there was no difference between NMOSD, migraine, and healthy controls. This was also true when adjusted for age, sex, and the intracranial volume. In contrast to NMOSD, the choroid plexus volume in MS was associated with the number of T2-weighted lesions in a linear model adjusted for age, sex, total intracranial volume, disease duration, relapses in the year before MRI, disease course, Expanded Disability Status Scale score, disease-modifying treatment, and treatment duration (beta 4.4; 95% CI 0.78–8.1; p = 0.018). Discussion This study supports an involvement of the choroid plexus in MS in contrast to NMOSD and provides clues to better understand the respective pathogenesis.

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. REGISTRATION: URL: https://clinicaltrials.gov ; Unique identifier: NCT02866838.

In spite of efforts to employ risk-based strategies to increase monitoring efficiency in the academic setting, empirical evidence on their effectiveness remains sparse. This mixed-methods study aimed to evaluate the risk-based on-site monitoring approach currently followed at our academic institution. We selected all studies monitored by the Clinical Trial Unit (CTU) according to Risk ADApted MONitoring (ADAMON) at the University Hospital Basel, Switzerland, between 01.01.2012 and 31.12.2014. We extracted study characteristics and monitoring information from the CTU Enterprise Resource Management system and from monitoring reports of all selected studies. We summarized the data descriptively. Additionally, we conducted semi-structured interviews with the three current CTU monitors. During the observation period, a total of 214 monitoring visits were conducted in 43 studies resulting in 2961 documented monitoring findings. Our risk-based approach predominantly identified administrative (46.2%) and patient right findings (49.1%). We identified observational study design, high ADAMON risk category, industry sponsorship, the presence of an electronic database, experienced site staff, and inclusion of vulnerable study population to be factors associated with lower numbers of findings. The monitors understand the positive aspects of a risk-based approach but fear missing systematic errors due to the low frequency of visits. We show that the factors mostly increasing the risk for on-site monitoring findings are underrepresented in the current risk analysis scheme. Our risk-based on-site approach should further be complemented by centralized data checks, allowing monitors to transform their role towards partners for overall trial quality, and success.

To describe how stroke survivors with atrial fibrillation implement direct oral anticoagulant treatment and propose appropriate metrics to describe adherence. Stroke patients with atrial fibrillation electronically recorded their self-administered direct oral anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban) during a 6-month observation phase after hospitalisation for ischemic stroke. Taking and timing adherence, correct dosing days, drug holidays, time of the day and day of the week subsets, dose-to-dose intervals and longest intervals between two consecutive doses were calculated from electronic monitoring data to describe and discuss the implementation phase of adherence. Data from 41 patients were analysed. Median age was 77 (IQR = 69-84), 63.4% were male and the majority suffered a mild stroke (median NIHSS: 1). Mean taking and timing adherence exceeded 90%. Correct dosing occurred in 86.6% of the days. Seven patients (17.1%) had intake pauses of three or more consecutive days. Patients with twice-daily regimen (70.7%) had higher taking adherence in the morning than in the evening (94.4% versus 89.9%; p = 0.001). No therapy- or anamneses-related characteristic was associated with taking adherence. Although adherence to direct oral anticoagulants of stroke patients with atrial fibrillation exceeded 90%, deviant intake patterns such as drug holidays and missed evening doses were common and raise concerns. Appropriate adherence metrics calculated from electronic monitoring data may guide healthcare professionals elucidating patient-tailored adherence-enhancing interventions. ClinicalTrials.gov registration number: NCT03344146.

Clinical studies in children are necessary yet conducting multiple visits at study centers remains challenging. The success of “care-at-home” initiatives and remote clinical trials suggests their potential to facilitate conduct of pediatric studies. This pilot aimed to study the feasibility of remotely collecting valid (i.e. complete and correct) saliva samples and clinical data utilizing mobile technology. Single-center, prospective pilot study in children undergoing elective tonsillectomy at the University of Basel Children’s Hospital. Data on pain scores and concomitant medication and saliva samples were collected by caregivers on two to four inpatient study days and on three consecutive study days at home. A tailored mobile application developed for this study supported data collection. The primary endpoint was the proportion of complete and correct caregiver-collected data (pain scale) and saliva samples in the at-home setting. Secondary endpoints included the proportion of complete and correct saliva samples in the inpatient setting, subjective feasibility for caregivers, and study cost. A total number of 23 children were included in the study of which 17 children, median age 6.0 years (IQR 5.0, 7.4), completed the study. During the at-home phase, 71.9% [CI = 64.4, 78.6] of all caregiver-collected pain assessments and 53.9% [CI = 44.2, 63.4] of all saliva samples were complete and correct. Overall, 64.7% [CI = 58.7, 70.4] of all data collected by caregivers at home was complete and correct. The predominant reason for incorrectness of data was adherence to the timing of predefined patient actions. Participating caregivers reported high levels of satisfaction and willingness to participate in similar trials in the future. Study costs for a potential sample size of 100 patients were calculated to be 20% lower for the at-home than for a traditional in-patient study setting. Mobile device supported studies conducted at home may provide a cost-effective approach to facilitate conduct of clinical studies in children. Given findings in this pilot study, data collection at home may focus on electronic data capture rather than biological sampling.