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Abstract Background Postoperative delirium (POD) is the most common neurological adverse event among elderly patients undergoing surgery. POD is associated with an increased risk for postoperative complications, long-term cognitive decline, an increase in morbidity and mortality as well as extended hospital stays. Delirium prevention and treatment options are currently limited. This study will evaluate the effect of transcranial electrical stimulation (tES) on the incidence of POD. Methods We will perform a randomized, double-blind, sham-controlled trial using single-session postoperative application of tES in the recovery room in 225 patients (> 65 years) undergoing elective major surgery. Patients will be randomly allocated (ratio 1:1:1) to one of three study groups: (1) alpha-tACS over posterior parietal cortex [2 mA, 20 min], (2) anodal tDCS over left dorsolateral prefrontal cortex [2 mA, 20 min], (3) sham [2 mA, 30 s]. Delirium will be screened twice daily with the 3-min diagnostic interview Confusion Assessment Method (3D-CAM) in the 5 days following surgery. The primary outcome is the incidence of POD defined as at least one positive screening during the five first postoperative days compared between tACS and sham groups. Secondary outcomes include delirium severity, duration, phenotype, postoperative pain, postoperative nausea and vomiting, electroencephalographic (EEG) markers, and fluid biomarkers. Discussion If effective, tES is a novel, easily applicable, non-invasive method to prevent the occurrence of POD. The comprehensive neurophysiological and biofluid assessments for markers of (neuro-)inflammation and neurodegeneration will shed light on the pathomechanisms behind POD and further elucidate the (after-)effects of tES. The potential implications for the postoperative recovery comprise enhanced patient safety, neurocognitive outcome, perioperative manageability but also reduced healthcare costs. Trial registration German Clinical Trial Registry DRKS00033703. Registered on February 23, 2024.

PurposeA relative afferent pupillary defect (RAPD) is a characteristic clinical sign of optic neuritis (ON). Here, we systematically evaluated ultrasound pupillometry (UP) for the detection of an RAPD in patients with ON, including a comparison with infrared video pupillometry (IVP), the gold standard for objective pupillometry.Materials and methodsWe enrolled 40 patients with acute (n = 9) or past (n = 31) ON (ON+), 31 patients with multiple sclerosis (MS) without prior ON, and 50 healthy controls (HC) in a cross-sectional observational study. Examinations comprised the swinging flashlight test, B-mode UP, IVP, autorefraction to assess the best-corrected visual acuity, optical coherence tomography to determine peripapillary retinal nerve fiber layer thickness, and the 51-item National Eye Institute-Visual Function Questionnaire to determine the vision-related quality of life.ResultsWhile UP and IVP measurements of pupil diameter (PD) at rest correlated in ON+ eyes (n = 52, r = 0.56, 95% CI: 0.35; 0.72) and in HC eyes (n = 100, r = 0.60, 95% CI: 0.47; 0.72), PD at rest was smaller in UP than in IVP measurements (difference, mean (SD) ON+ eyes: 0.44 (0.87) mm, HC eyes: 0.69 (0.80) mm). RAPD assessment by UP sharply discriminated acute ON eyes (n = 9) and HC eyes (n = 100, AUC = 1, 95%CI: 1; 1). UP detected an RAPD in 5/31 (16%) patients with MS without prior ON who had not exhibited an RAPD during the swinging flashlight test. In ON+ eyes (n = 52), UP showed stronger correlations with visual acuity (r = 0.66, 95% CI: 0.50; 0.78) and vision-related quality of life (r = 0.47, 95% CI: 0.24; 0.66) than IVP (r = 0.52, 95% CI: 0.36; 0.67 and r = 0.27, 95% CI: 0.03; 0.51).ConclusionsB-mode UP allows for objective detection and quantification of an RAPD with performance characteristics similar to IVP. RAPD assessment by UP may detect subclinical optic nerve damage in patients with MS. We propose a standardized protocol for RAPD detection by UP that can be used in routine clinical evaluation of patients with ON or other optic neuropathies.

Background Oral anticoagulation (OAC) is key in stroke prevention in patients with atrial fibrillation (AF) but there is uncertainty regarding the optimal timing of OAC (re)initiation after stroke, as recent large randomised controlled trials have methodological weaknesses and excluded stroke patients on therapeutic anticoagulation at stroke onset as well as patients started on a vitamin K antagonist after stroke. The ‘1–3–6–12 days rule’, based on expert consensus and referring to stroke severity, was used in clinical practice to initiate OAC after acute ischaemic stroke or transient ischaemic attack (TIA) since publication in 2013.Methods We retrospectively assessed whether compliance to the ‘1–3–6–12 days rule’ was associated with the composite endpoint (recurrent stroke, systemic embolism, myocardial infarction, major bleeding or all-cause death).Results Among 708 registry patients with known AF before stroke and hospitalisation within 72 hours after stroke, 432 were anticoagulated at stroke onset. OAC was started according to the ‘1–3–6–12 days rule’ in 255 (39.2%) patients. Non-adherence to the ‘1–3–6–12 days rule’ was not associated with the composite endpoint within 3 months in 661 patients who (re-)started on OAC (log-rank test: p=0.74).Results were similar for 521 patients (re)started on a non-vitamin K-dependent OAC.Conclusion (Re)starting OAC after stroke followed the ‘1–3–6–12 days rule’ in about 40% of all patients with AF, and more often in those anticoagulated at stroke onset. Adherence to the ‘1–3–6–12 days rule’ did not reduce the composite clinical endpoint, if OAC was restarted within 3 months of stroke/TIA.Trial registration number NCT02306824.

Drawing upon Heron and Reason's (1997) participatory inquiry paradigm and extended epistemology, this article explores how six Master of Social Work (MSW) students engaged in sensory arts-based critical reflection concerning their social location, identities, social justice, and social policy. We share our process for creating sensory arts-based stories, the stories themselves, and pedagogical reflections. We elucidate how sensory arts-based storytelling allows learners to draw upon their strengths, unique perspectives, and experiences in the world, generating transformative understandings of social justice. Sensory arts-based storytelling holds potential as an interdisciplinary mode of critical reflection, generating inclusive learning environments oriented towards social change. [This article was co-authored by The Social Justice Learning Collaborative.]

In addition to loss of sensory and motor function below the level of the lesion, traumatic spinal cord injury (SCI) may reduce circulating steroid hormones that are necessary for maintaining normal physiological function for extended time periods. For men, who comprise nearly 80% of new SCI cases each year, testosterone is the most abundant circulating sex steroid. SCI often results in significantly reduced testosterone production and may result in chronic low testosterone levels. Testosterone plays a role in respiratory function and the expression of respiratory neuroplasticity. When testosterone levels are low, young adult male rats are unable to express phrenic long-term facilitation (pLTF), an inducible form of respiratory neuroplasticity invoked by acute, intermittent hypoxia (AIH). However, testosterone replacement can restore this respiratory neuroplasticity. Complicating the interpretation of this finding is that testosterone may exert its influence in three possible ways: 1) directly through androgen receptor (AR) activation, 2) through conversion to dihydrotestosterone (DHT) by way of the enzyme 5α-reductase, or 3) through conversion to 17β-estradiol (E2) by way of the enzyme aromatase. DHT signals via AR activation similar to testosterone, but with higher affinity, while E2 activates local estrogen receptors. Evidence to date supports the idea that exogenous testosterone supplementation exerts its influence through estrogen receptor signaling under conditions of low circulating testosterone. Here we explored both recovery of breathing function (measured with whole body barometric plethysmography) and the expression of AIH-induced pLTF in male rats following C2-hemisection SCI. One week post injury, rats were supplemented with either E2 or DHT for 7 days. We hypothesized that E2 would enhance ventilation and reveal pLTF following AIH in SCI rats. To our surprise, though E2 did beneficially impact overall breathing recovery following C2-hemisection, both E2 supplementation and DHT restored the expression of AIH-induced pLTF 2 weeks post-SCI.

Abstract Introduction Various developments result in increasing workloads in general practices. New models of care and a restructuring of the division of tasks could provide relief. One approach is to extend the delegation of medical tasks from general practitioners (GPs) to medical practice assistants (MPAs). So far, there has been a lack of information about specific situations in which patients are willing to be treated exclusively by MPAs. Methods In three German federal states, patients who visited a general practice were surveyed exploratively and cross-sectionally with a self-designed, paper-based questionnaire. The data were analysed descriptively and multivariate. A mixed binary logistic regression model was calculated to account for cluster effects at practice level (random intercept model). The dependent variable was patients' acceptance of task delegation. Results A total of 1861 questionnaires from 61 general practices were included in the analysis. Regarding the current problem/request, a total of 30% of respondents could imagine being treated only by MPAs. Regarding theoretical reasons for consultation, more than half of the patients agreed to be treated by MPAs. According to the regression model, MPAs were preferred when patients were younger (10-year OR = 0.84, 95%-CI [0.75, 0.93]) or had a less complicated issue (OR = 0.44, 95%-CI [0.26, 0.8]). For four current problems/requests (“acute complaints” OR = 0.27, 95%-CI [0.17, 0.45], “routine health check” OR = 0.48, 95%-CI [0.3, 0.79], “new problem” OR = 0.13, 95%-CI [0.06, 0.28], “known problem” OR = 0.16, 95%-CI [0.1, 0.27]) patients prefer to be treated by GPs instead of MPAs. Discussion For the first time, statements could be made on patients’ acceptance of task delegation in relation to current and theoretical reasons for treatment in general practices in Germany. The discrepancy in response behaviour on a theoretical and individual level could be explained by different contexts of questions and differences at practice level. Overall, patients seem to be open to increased delegation of medical tasks, depending on the reason for treatment. Selection and response biases should be considered in the interpretation. Conclusion The results are not completely opposed to an extension of task delegation. Further interventional studies could provide information on the possible effects of expansion of delegable tasks.

Abstract Background The extent of resection of glioma is one of the most important predictors of the survival duration of patients after surgery. The presence of eloquent areas within or near a tumor often limits resection, as resection of these areas would result in functional loss and reduced quality of life. The aim of this randomized, triple-blind, sham-controlled study is to investigate the capability of repetitive navigated transcranial magnetic stimulation (rnTMS) over the primary motor cortex to facilitate the functional reorganization of the motor network. Methods One hundred forty-eight patients with tumors in movement-relevant areas will be included in this randomized, sham-controlled, bicentric, triple-blind clinical trial. Patients considered at high risk for postoperative motor deficits according to an initial nTMS assessment will receive inhibitory rnTMS at 1 Hz for 30 min followed by a short motor training of 10 min. Stimulation will be applied to the fiber endings of the corticospinal tract closest to the tumor based on individualized tractography. Stimulation will be performed twice daily for each 30 min for 5–28 days depending on the individually available time between study inclusion and surgery. The intervention is controlled by a sham stimulation group (1:1 randomization), where a plastic adapter will be placed on the coil. We expect a comparable or better motor status 3 months postoperatively as measured by the British Medical Research Council (BMRC) score for the affected upper extremity (non-inferiority) and a higher rate of gross total resections (superiority) in the rnTMS compared to the sham group. Discussion The generated reorganization of the brain’s areas for motor function should allow a more extensive and safer removal of the tumor while preserving neurological and motor function. This would improve both survival and quality of life of our patients. Trial registration DRKS.de DRKS00017232 . Registered on 28 January 2020.

In the face of ongoing interpersonal and structural violence towards sex workers in Canada, this research inquiry explores nine women and gender-diverse sex workers’ experiences of place identity within their workplaces. Employing multisensory and arts-based ethnographic fieldwork, the co-researchers storied their embodied place-based experiences of identity. The research findings illuminate place-identity processes within sex workplaces, suggesting that the context, materiality, and multisensory atmospheres of the co-researchers’ work environments were entwined with internal and external self-concepts. The co-researchers created personalized multisensory atmospheres in their workplaces through the use of colour, visual art, and music. Having workplaces that positively supported place identity fostered workplace comfort, control, and empowerment. Ultimately, this research suggests that place-identity processes in sex workplaces have the possibility to resist and shift sex work stigma.

ObjectiveSurgical resection of motor eloquent tumors poses the risk of causing postoperative motor deficits which leads to reduced quality of life in these patients. Currently, rehabilitative procedures are limited with physical therapy being the main treatment option. This study investigated the efficacy of repetitive navigated transcranial magnetic stimulation (rTMS) for treatment of motor deficits after supratentorial tumor resection.MethodsThis randomized, double-blind, sham-controlled trial (DRKS00010043) recruited patients with a postoperatively worsened upper extremity motor function immediately postoperatively. They were randomly assigned to receive rTMS (1Hz, 110% RMT, 15 minutes, 7 days) or sham stimulation to the motor cortex contralateral to the injury followed by physical therapy. Motor and neurological function as well as quality of life were assessed directly after the intervention, one month and three months postoperatively.ResultsThirty patients were recruited for this study. There was no significant difference between both groups in the primary outcome, the Fugl Meyer score three months postoperatively [Group difference (95%-CI): 5.05 (-16.0; 26.1); p=0.631]. Patients in the rTMS group presented with better hand motor function one month postoperatively. Additionally, a subgroup of patients with motor eloquent ischemia showed lower NIHSS scores at all timepoints.ConclusionsLow-frequency rTMS facilitated the recovery process in stimulated hand muscles, but with limited generalization to other functional deficits. Long-term motor deficits were not impacted by rTMS. Given the reduced life expectancy in these patients a shortened recovery duration of deficits can still be of high significance.Clinical Trial Registrationhttps://drks.de/DRKS00010043.

IntroductionAcute ischemic stroke (AIS) is a time-critical medical emergency. For patients with large-vessel occlusions (LVO), mechanical thrombectomy (MT) is the gold-standard treatment. Mobile Stroke Units (MSUs) provide on-site diagnostic capabilities via computed tomography (CT) and have been shown to improve functional outcomes in stroke patients, but are cost-efficient only in urban areas. Blood biomarkers have recently emerged as possible alternative to cerebral imaging for LVO diagnosis. Prehospital LVO diagnosis offers the potential to transport patients directly to centers that have MT treatment available. In this study, we assess the accuracy of combining two biomarkers, HFABP and NT-proBNP, with clinical indicators to detect LVO using ultra-early prehospital blood samples. The study was registered in the German Clinical Trials Register (DRKS-ID: DRKS00030399).Methods and analysisWe plan a multicenter prospective observational study with 800 patients with suspected stroke enrolled within 24 h of symptom onset. Study participants will be recruited at three sites (MSUs) in Berlin, Germany. Blood-samples will be taken pre-hospitally at the scene and tested for HFABP and NT-proBNP levels. Additional clinical data and information on final diagnosis will be collected and documented in an electronic case report form (eCRF). Sensitivity and specificity of the combination will be calculated through iterative permutation-response calculations.DiscussionThis study aims to evaluate the diagnostic capabilities of a combination of the biomarkers HFABP and NT-proBNP in LVO prediction. In contrast to most other biomarker studies to date, by employing MSUs as study centers, ultra-early levels of biomarkers can be analyzed. Point-of-care LVO detection in suspected stroke could lead to faster treatment in both urban and rural settings and thus improve functional outcomes on a broader scale.Clinical trial registrationDeutsches Register klinischer Studien https://drks.de/search/de/trial/DRKS00030399, DRKS00030399

Abstract The combination of repeated behavioral training with transcranial direct current stimulation (tDCS) holds promise to exert beneficial effects on brain function beyond the trained task. However, little is known about the underlying mechanisms. We performed a monocenter, single-blind randomized, placebo-controlled trial comparing cognitive training to concurrent anodal tDCS (target intervention) with cognitive training to concurrent sham tDCS (control intervention), registered at ClinicalTrial.gov (Identifier NCT03838211). The primary outcome (performance in trained task) and secondary behavioral outcomes (performance on transfer tasks) were reported elsewhere. Here, underlying mechanisms were addressed by pre-specified analyses of multimodal magnetic resonance imaging before and after a three-week executive function training with prefrontal anodal tDCS in 48 older adults. Results demonstrate that training combined with active tDCS modulated prefrontal white matter microstructure which predicted individual transfer task performance gain. Training-plus-tDCS also resulted in microstructural grey matter alterations at the stimulation site, and increased prefrontal functional connectivity. We provide insight into the mechanisms underlying neuromodulatory interventions, suggesting tDCS-induced changes in fiber organization and myelin formation, glia-related and synaptic processes in the target region, and synchronization within targeted functional networks. These findings advance the mechanistic understanding of neural tDCS effects, thereby contributing to more targeted neural network modulation in future experimental and translation tDCS applications.

Introduction Wheezing is common in preschool children and its clinical assessment often challenging for caretakers. This study aims to evaluate the impact of a novel digital wheeze detector (WheezeScan™) on disease control in a home care setting. Methods A multicentre randomised open-label controlled trial was conducted in Berlin, Istanbul and London. Participants aged 4–84 months with a doctor's diagnosis of recurrent wheezing in the past 12 months were included. While the control group followed usual care, the intervention group received the WheezeScan™ for at-home use for 120 days. Parents completed questionnaires regarding their child's respiratory symptoms, disease-related and parental quality of life, and caretaker self-efficacy at baseline (T0), 90 days (T1) and 4 months (T2). Results A total of 167 children, with a mean±sd age of 3.2±1.6 years, were enrolled in the study (intervention group n=87; control group n=80). There was no statistically significant difference in wheeze control assessed by TRACK (mean difference 3.8, 95% CI −2.3–9.9; p=0.2) at T1 between treatment groups (primary outcome). Children's and parental quality of life and parental self-efficacy were comparable between both groups at T1. The evaluation of device usability and perception showed that parents found it useful. Conclusion In the current study population, the wheeze detector did not show significant impact on the home management of preschool wheezing. Hence, further research is needed to better understand how the perception and usage behaviour may influence the clinical impact of a digital support.

BackgroundMyasthenia gravis (MG) is a rare autoimmune disease and chronic condition that necessitates specialized care. Patients experience a significant burden of disease affecting various aspects of their lives. The aim of this study was to investigate the impact of MG on family planning, challenges associated with pregnancy, childcare responsibilities and the extent to which MG patients perceive and utilize social support.MethodsThis analysis used data from our main data of a large cross-sectional study built on a questionnaire-based survey encompassing 1,660 MG patients and members of the German Myasthenia Association (Deutsche Myasthenie Gesellschaft), and focused on sociodemographic, clinical and family planning relevant data points.ResultsDecisions regarding family planning were significantly impacted for individuals with MG when MG symptoms started either before or during their family planning (men: n = 19 and 29.7%; women: n = 156 and 58.4%). In this subgroup a substantial proportion opted against parenthood due to MG (men: n = 8 and 50.0%; women: n = 54 and 38.0% and/or another n = 12 and 8.4% of female participants encountered partner-related refusals). In the subgroup of female SP with MG starting before or during family planning who have reported ever been pregnant the self-reported miscarriage rate was 29.0% (n = 51). MG patients with medium incomes or moderate disease severity reported lower levels of perceived social support. 42.7% (n = 606) of participants needed assistance in negotiations with health insurers and 28.0% (n = 459) needed support for transportation to medical appointments.ConclusionThis study shows a significant impact of MG on family planning decisions, affecting both women and men, and often resulting in life-altering decisions such as voluntary childlessness due to MG. The significance of social support becomes evident as a vital factor, especially when navigating through the healthcare system. Tailored healthcare approaches, organized guidance and comprehensive support is needed to enable informed decision-making and offer assistance for MG patients.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT03979521, Registered 7 June 2019 (retrospectively registered).

Abstract Background Fragmented and complex healthcare systems make it difficult to provide continuity of care for patients with advanced cancer near the end of life. Nurse‐based cross‐sectoral navigation support has the potential to increase patients' quality of life. The objective of this paper was to evaluate associations between navigation support and health care utilization, and the associated costs of care. Methods The evaluation is based on claims data from 37 statutory health insurance funds. Non‐randomized recruitment of the intervention group (IG) took place between 2018 and 2019 in four German hospitals. The comparison group (CG) was defined ex post. It comprises nonparticipating clients of the involved health insurance funds matched on age, gender, and diagnosis in a 1:4 ratio to the IG. Healthcare resource utilization was compared using incident rate ratios (IRRs) based on negative binomial regression models. Linear mixed models were performed to compare differences in lengths of hospital stays and costs between groups. Results A total of 717 patients were included (IG: 149, CG: 568). IG patients showed shorter average lengths of hospital stays (IG: 11 days [95% CI: 10, 13] vs. CG: 15 days [95% CI: 14, 16], p

Introduction The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular (CV) disease progression by comprehensively investigating a high-risk patient population with different organ manifestations.Methods and analysis A total of 8000 adult patients will be recruited who have either suffered an acute CV event (CVE) requiring hospitalisation or who have not experienced a recent acute CVE but are at high CV risk. An initial study examination is performed during the acute treatment phase of the index CVE or after inclusion into the chronic high risk arm. Deep phenotyping is then performed after ~90 days and includes assessments of the patient’s medical history, health status and behaviour, cardiovascular, nutritional, metabolic, and anthropometric parameters, and patient-related outcome measures. Biospecimens are collected for analyses including ‘OMICs’ technologies (e.g., genomics, metabolomics, proteomics). Subcohorts undergo MRI of the brain, heart, lung and kidney, as well as more comprehensive metabolic, neurological and CV examinations. All participants are followed up for up to 10 years to assess clinical outcomes, primarily major adverse CVEs and patient-reported (value-based) outcomes. State-of-the-art clinical research methods, as well as emerging techniques from systems medicine and artificial intelligence, will be used to identify associations between patient characteristics, longitudinal changes and outcomes.Ethics and dissemination The study was approved by the Charité—Universitätsmedizin Berlin ethics committee (EA1/066/17). The results of the study will be disseminated through international peer-reviewed publications and congress presentations.Study registration First study phase: Approved WHO primary register: German Clinical Trials Register: https://drks.de/search/de/trial/DRKS00016852; WHO International Clinical Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00016852. Recruitment started on July 18, 2017.Second study phase: Approved WHO primary register: German Clinical Trials Register DRKS00023323, date of registration: November 4, 2020, URL: http://www.drks.de/ DRKS00023323. Recruitment started on January 1, 2021.

Remembering objects and their associated location (object–location memory; OLM), is a fundamental cognitive function, mediated by cortical and subcortical brain regions. Previously, the combination of OLM training and transcranial direct current stimulation (tDCS) suggested beneficial effects, but the evidence remains heterogeneous. Here, we applied focal tDCS over the right temporoparietal cortex in 52 participants during a two-day OLM training, with anodal tDCS (2 mA, 20 min) or sham (40 s) on the first day. The focal stimulation did not enhance OLM performance on either training day (stimulation effect: −0.09, 95%CI: [−0.19; 0.02], p = 0.08). Higher electric field magnitudes in the target region were not associated with individual performance benefits. Participants with content-related learning strategies showed slightly superior performance compared to participants with position-related strategies. Additionally, training gains were associated with individual verbal learning skills. Consequently, the lack of behavioral benefits through focal tDCS might be due to the involvement of different cognitive processes and brain regions, reflected by participant’s learning strategies. Future studies should evaluate whether other brain regions or memory-relevant networks may be involved in the modulation of object–location associations, investigating other target regions, and further exploring individualized stimulation parameters.

Abstract Purpose Given the psychosocial burdens patients in advanced stages of cancer face, innovative care concepts are needed. At the same time, such vulnerable patient groups are difficult to reach for participation in intervention studies and randomized patient inclusion may not be feasible. This article aims to identify systematic biases respectively selection effects occurring during the recruitment phase and to discuss their potential causes based on a non-randomized, multicenter intervention study with patients in advanced stages of cancer. Methods Patients diagnosed with at least one of 16 predefined cancers were recruited at four hospitals in three German cities. The effect of social care nurses’ continuous involvement in acute oncology wards was measured by health-related quality of life (EORTC QLQ-C30), information and participation preferences, decisional conflicts, doctor-patient communication, health literacy and symptom perception. Absolute standardized mean difference was calculated as a standardized effect size to test baseline characteristics balance between the intervention and control groups. Results The study enrolled 362 patients, 150 in the intervention and 212 in the control group. Except for gender, both groups differed in relevant socio-demographic characteristics, e.g. regarding age and educational background. With respect to the distribution of diagnoses, the intervention group showed a higher symptom burden than the control group. Moreover, the control group reported better quality of life at baseline compared to the intervention group (52.6 points (SD 21.7); 47.8 points (SD 22.0), ASMD = 0.218, p = 0.044). Conclusion Overall, the intervention group showed more social and health vulnerability than the control group. Among other factors, the wide range of diagnoses included and structural variation between the recruiting clinics increased the risk for bias. We recommend a close, continuous monitoring of relevant social and health-related characteristics during the recruitment phase as well as the use of appropriate statistical analysis strategies for adjustment, such as propensity score methods. Trial registration: German Clinical Trials Register (DRKS-ID: DRKS00013640 ); registered on 29th December 2017.

Purpose: A relative afferent pupillary defect (RAPD) is a characteristic clinical sign of optic neuritis (ON). Here, we systematically evaluated ultrasound pupillometry (UP) for the detection of an RAPD in patients with ON, including a comparison with infrared video pupillometry (IVP), the gold standard for objective pupillometry. Materials and methods: We enrolled 40 patients with acute (n = 9) or past (n = 31) ON (ON+), 31 patients with multiple sclerosis (MS) without prior ON, and 50 healthy controls (HC) in a cross-sectional observational study. Examinations comprised the swinging flashlight test, B-mode UP, IVP, autorefraction to assess the best-corrected visual acuity, optical coherence tomography to determine peripapillary retinal nerve fiber layer thickness, and the 51-item National Eye Institute-Visual Function Questionnaire to determine the vision-related quality of life. Results: While UP and IVP measurements of pupil diameter (PD) at rest correlated in ON+ eyes (n = 52, r = 0.56, 95% CI: 0.35; 0.72) and in HC eyes (n = 100, r = 0.60, 95% CI: 0.47; 0.72), PD at rest was smaller in UP than in IVP measurements (difference, mean (SD) ON+ eyes: 0.44 (0.87) mm, HC eyes: 0.69 (0.80) mm). RAPD assessment by UP sharply discriminated acute ON eyes (n = 9) and HC eyes (n = 100, AUC = 1, 95%CI: 1; 1). UP detected an RAPD in 5/31 (16%) patients with MS without prior ON who had not exhibited an RAPD during the swinging flashlight test. In ON+ eyes (n = 52), UP showed stronger correlations with visual acuity (r = 0.66, 95% CI: 0.50; 0.78) and vision-related quality of life (r = 0.47, 95% CI: 0.24; 0.66) than IVP (r = 0.52, 95% CI: 0.36; 0.67 and r = 0.27, 95% CI: 0.03; 0.51). Conclusions: B-mode UP allows for objective detection and quantification of an RAPD with performance characteristics similar to IVP. RAPD assessment by UP may detect subclinical optic nerve damage in patients with MS. We propose a standardized protocol for RAPD detection by UP that can be used in routine clinical evaluation of patients with ON or other optic neuropathies. [ABSTRACT FROM AUTHOR]

Background: Postoperative delirium (POD) is the most common neurological adverse event among elderly patients undergoing surgery. POD is associated with an increased risk for postoperative complications, long-term cognitive decline, an increase in morbidity and mortality as well as extended hospital stays. Delirium prevention and treatment options are currently limited. This study will evaluate the effect of transcranial electrical stimulation (tES) on the incidence of POD. Methods: We will perform a randomized, double-blind, sham-controlled trial using single-session postoperative application of tES in the recovery room in 225 patients (> 65 years) undergoing elective major surgery. Patients will be randomly allocated (ratio 1:1:1) to one of three study groups: (1) alpha-tACS over posterior parietal cortex [2 mA, 20 min], (2) anodal tDCS over left dorsolateral prefrontal cortex [2 mA, 20 min], (3) sham [2 mA, 30 s]. Delirium will be screened twice daily with the 3-min diagnostic interview Confusion Assessment Method (3D-CAM) in the 5 days following surgery. The primary outcome is the incidence of POD defined as at least one positive screening during the five first postoperative days compared between tACS and sham groups. Secondary outcomes include delirium severity, duration, phenotype, postoperative pain, postoperative nausea and vomiting, electroencephalographic (EEG) markers, and fluid biomarkers. Discussion: If effective, tES is a novel, easily applicable, non-invasive method to prevent the occurrence of POD. The comprehensive neurophysiological and biofluid assessments for markers of (neuro-)inflammation and neurodegeneration will shed light on the pathomechanisms behind POD and further elucidate the (after-)effects of tES. The potential implications for the postoperative recovery comprise enhanced patient safety, neurocognitive outcome, perioperative manageability but also reduced healthcare costs. Trial registration: German Clinical Trial Registry DRKS00033703. Registered on February 23, 2024. [ABSTRACT FROM AUTHOR]