Treatment with add-on IVIg in Myositis Early In the diSease course May be sUperior to Steroids alone for reaching CLinical improvEment (TIME IS MUSCLE): study protocol of a phase-2 double-blind placebo-controlled randomised trial.

INTRODUCTION: For idiopathic inflammatory myopathies (IIM) ('myositis') standard initial treatment is high-dosed glucocorticoids, which results in relatively slow improvement of muscle strength. Early immunosuppression or modulation by intensive treatment ('hit-early, hit-hard') may induce faster reduction of disease activity and prevent chronic disability due to disease-induced structural muscle damage. Intravenous immunoglobulin (IVIg) in addition to standard glucocorticoid treatment may be promising in this regard as was shown in various studies: add-on IVIg improved symptoms and muscle strength in refractory myositis patients and monotherapy IVIg improved outcomes after 9 weeks, in about half of treatment-naive patients. HYPOTHESIS: We hypothesise that early add-on IVIg leads to a greater clinical response after 12 weeks in patients with newly diagnosed myositis, in comparison to prednisone monotherapy. Second, we expect that early treatment with add-on IVIg leads to a faster time to improvement and sustained positive effects on multiple secondary outcomes. METHODS: The Time Is Muscle trial is a phase-2 double-blind placebo-controlled randomised trial. Forty-eight patients with IIM will be treated with IVIg or placebo at baseline (within 1 week after diagnosis) and after 4 and 8 weeks, in addition to standard therapy with prednisone. The primary outcome is the Total Improvement Score (TIS) of the myositis response criteria at 12 weeks. At baseline, and after 4, 8, 12, 26 and 52 weeks, relevant secondary outcomes will be assessed, including time to moderate improvement (TIS≥40), mean daily prednisone dosage, physical activity, health-related quality of life, fatigue and MRI muscle imaging parameters. ETHICS AND DISSEMINATION: Ethical approval was obtained from the medical ethics committee of the Academic Medical Centre, University of Amsterdam, the Netherlands (2020_180; including a first amendment approval at the 12 April 2023; A2020_180_0001). The results will be distributed through conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: EU Clinical trials register (2020-001710-37).

Multimodality Screening For (Peri)Myocarditis In Newly Diagnosed Idiopathic Inflammatory Myopathies: A Cross-Sectional Study.

BACKGROUND: Cardiac involvement in idiopathic inflammatory myopathy (IIM or "myositis") is associated with an approximate 4% mortality, but standardised screening strategies are lacking. OBJECTIVE: We explored a multimodality screening on potentially reversible cardiac involvement -i.e. active (peri)myocarditis -in newly diagnosed IIM. METHODS: We included adult IIM patients from 2017 to 2020. At time of diagnosis, patients underwent cardiac evaluation including laboratory biomarkers, electrocardiography, echocardiography, and cardiac magnetic resonance imaging (CMR). Based on 2019 consensus criteria for myocarditis, an adjudication committee made diagnoses of definite, probable, possible or no (peri)myocarditis. We explored diagnostic values of sequentially added diagnostic modalities by Constructing Classification and Regression Tree (CART) analysis in patients with definite/probable versus no (peri)myocarditis. RESULTS: We included 34 IIM patients, in whom diagnoses of definite (six, 18%), probable (two, 6%), possible (11, 32%), or no (peri)myocarditis (15, 44%) were adjudicated. CART-analysis showed high-sensitivity cardiac troponin T (cut-off value < 2.3 times the upper limit of normal (xULN)) ruled out (peri)myocarditis with a sensitivity of 88%, while high-sensitivity troponin I (cut-off value > 2.9 xULN for females and > 1.8 xULN for males) ruled in (peri)myocarditis with a specificity of 100%. Applying high-sensitivity cardiac troponins with these cut-off values in a diagnostic algorithm without and with a CMR to the total population of 34 patients demonstrated a diagnostic accuracy for a clear diagnosis of probable/definite or no (peri)myocarditis of 59% and 68%, respectively. CONCLUSIONS: A diagnostic algorithm for detection of (peri)myocarditis in adult IIM may consist of sequential testing with high-sensitivity cardiac troponins and CMR.

B-cell receptor profiling before and after IVIG monotherapy in newly diagnosed idiopathic inflammatory myopathies.

OBJECTIVE: To unravel B-cell receptor (BcR) characteristics in muscle tissues and peripheral blood and gain more insight into BcR repertoire changes in peripheral blood in idiopathic inflammatory myopathies (IIMs), and study how this correlates to the clinical response to IVIG. METHODS: Nineteen treatment-naive patients with newly diagnosed IIM were prospectively treated with IVIG monotherapy. RNA-based BcR repertoire sequencing was performed in muscle biopsies collected before, and in peripheral blood (PB) collected before and nine weeks after IVIG treatment. Results were correlated to patients' clinical improvement based on the total improvement score (TIS). RESULTS: Prior to IVIG treatment, BcR clones found in muscle tissue could be retrieved in peripheral blood. Nine weeks after IVIG treatment, new patient-specific dominant BcR clones appeared in peripheral blood while pre-treatment dominant BcR clones disappeared. The cumulative frequency of all dominant BcR clones before treatment was significantly higher in individuals who responded to IVIG compared with those who did not respond to IVIG, and correlated with a higher CK. During follow-up, a decrease in the cumulative frequency of all dominant clones correlated with a higher TIS. CONCLUSION: In treatment-naive patients with newly diagnosed IIM, muscle tissue and peripheral blood share expanded BcR clones. In our study a higher cumulative frequency of dominant BcR clones in blood before treatment was associated with a higher CK and better treatment response, suggesting that response to IVIG may depend on the composition of the pre-treatment BcR repertoire.

Evaluating patient and neurosurgeon perspectives on virtualisation of neurosurgery clinics in the COVID-19 era: a prospective mirror survey study.

BACKGROUND: The COVID-19 pandemic has compelled a global shift in healthcare service delivery towards virtualisation, including in Neurosurgery. Our study aims to elucidate the patient and neurosurgeon perceptions of virtual neurosurgery consultations (VNCs) and formulate a guidance algorithm based on our experience. METHODS: Between June 2020 and December 2020, we prospectively surveyed patients and neurosurgeons following their VNCs using a 10-item survey (four qualitative and six five-point Likert scale questions). Non-parametric hypothesis testing and grounded coding with inter-coder agreement was used to analyse quantitative and qualitative data, respectively. RESULTS: 106 patients and 10 neurosurgeons completed the survey. Wilcoxon rank-sum test revealed a statistically significant difference between the neurosurgeon and patient responses (p < 0.001). Patients perceived VNCs benefits to be enhanced efficiency (n = 142) and communication (28); and VNCs drawbacks as safety (46), technological (32), and administration (15) issues. Neurosurgeons perceived VNCs benefits to be enhanced efficiency (13), reduced COVID-19 exposure (2); and VNCs drawbacks as examination practicality (14), technological (6), and concerns for patients (6). Neurosurgeons perceived the relative indications for VNCs as postoperative follow-up clinics, and scan result discussions; and relative contraindications as neuro-oncology, new patients, and patients with worsening neurological symptoms. CONCLUSIONS: Our mirror-survey study provides preliminary evidence that VNCs render increased efficiency, communication, and safety in the current COVID-19 era. Going forward, we believe that further improvements in technology and administration are necessary, greater neurosurgeon appreciation of the patient-perceived benefits of VNCs is required, and neurosurgeons are to exercise clinical discernment on when to use VNCs.Key PointsWhat are the perceptions of patient and consultant neurosurgeons towards virtual neurosurgery consultations (VNCs)?Patient-perceived benefits of VNCs: enhanced efficiency/communication; VNC drawbacks: safety, technological, and administration issues. Neurosurgeon-perceived VNCs benefits of VNCs: enhanced efficiency, reduced COVID-19 exposure; VNC drawbacks: examination practicality, technological, and concerns for patients.Post-operative reviews and scan result discussions are perceived relative indications for VNCs; whereas new patient consultations, neuro-oncology and patients with new-onset neurological deficits are perceived relative contraindications for VNCs.Improvement in technology and administration is necessary; greater neurosurgeon appreciation of patient-perceived VNCs benefits is required, and neurosurgeons are to exercise clinical discernment on when to use VNCs.

TCRß clones in muscle tissue share structural features in patients with idiopathic inflammatory myopathy and are associated with disease activity.

Objectives: To characterize the T cell receptor (TCRß) repertoire in peripheral blood and muscle tissues of treatment naïve patients with newly diagnosed idiopathic inflammatory myopathies (IIMs). Methods: High throughput RNA sequencing of the TCRß chain was performed in peripheral blood and muscle tissue in twenty newly-diagnosed treatment-naïve IIM patients (9 DM, 5 NM/OM, 5 IMNM and 1 ASyS) and healthy controls. Results thereof were correlated with markers of disease activity. Results: Muscle tissue of IIM patients shows more expansion of TCRß clones and decreased diversity when compared to peripheral blood of IIM as well as healthy controls (both p=0.0001). Several expanded TCRß clones in muscle are tissue restricted and cannot be retrieved in peripheral blood. These clones have significantly longer CDR3 regions when compared to clones (also) found in circulation (p=0.0002), while their CDR3 region is more hydrophobic (p<0.01). Network analysis shows that clonal TCRß signatures are shared between patients. Increased clonal expansion in muscle tissue is significantly correlated with increased CK levels (p=0.03), while it tends to correlate with decreased muscle strength (p=0.08). Conclusion: Network analysis of clones in muscle of IIM patients shows shared clusters of sequences across patients. Muscle-restricted CDR3 TCRß clones show specific structural features in their T cell receptor. Our results indicate that clonal TCRß expansion in muscle tissue might be associated with disease activity. Collectively, these findings support a role for specific clonal T cell responses in muscle tissue in the pathogenesis of the IIM subtypes studied.

Topologically associating domains are disrupted by evolutionary genome rearrangements forming species-specific enhancer connections in mice and humans.

Distinguishing between conserved and divergent regulatory mechanisms is essential for translating preclinical research from mice to humans, yet there is a lack of information about how evolutionary genome rearrangements affect the regulation of the immune response, a rapidly evolving system. The current model is topologically associating domains (TADs) are conserved between species, buffering evolutionary rearrangements and conserving long-range interactions within a TAD. However, we find that TADs frequently span evolutionary translocation and inversion breakpoints near genes with species-specific expression in immune cells, creating unique enhancer-promoter interactions exclusive to the mouse or human genomes. This includes TADs encompassing immune-related transcription factors, cytokines, and receptors. For example, we uncover an evolutionary rearrangement that created a shared LPS-inducible regulatory module between OASL and P2RX7 in human macrophages that is absent in mice. Therefore, evolutionary genome rearrangements disrupt TAD boundaries, enabling sequence-conserved enhancer elements from divergent genomic locations between species to create unique regulatory modules.

OptimisAtion of Diagnostic Accuracy in idioPathic inflammaTory myopathies (ADAPT study): a protocol for a prospective diagnostic accuracy study of multimodality testing in patients suspected of a treatable idiopathic inflammatory myopathy.

INTRODUCTION: Idiopathic inflammatory myopathies (IIMs) excluding inclusion body myositis (IBM) are a group of heterogeneous autoimmune disorders characterised by subacute-onset and progressive proximal muscle weakness, which are frequently part of a multisystem autoimmune disorder. Reaching the diagnosis can be challenging, and no gold standard for the diagnosis of IIM exists. Diagnostic modalities include serum creatine kinase activity, muscle imaging (MRI or ultrasound (US)), electromyography (EMG), myositis autoantibody testing and muscle biopsy. Several diagnostic criteria have been developed for IIMs, varying in reported sensitivity and specificity. HYPOTHESIS: We hypothesise that an evidence-based diagnostic strategy, using fewer and preferably the least invasive diagnostic modalities, can achieve the accuracy of a complete panel of diagnostic tests, including MRI, US, EMG, myositis-specific autoantibody testing and muscle biopsy. METHODS AND ANALYSIS: The OptimizAtion of Diagnostic Accuracy in idioPathic inflammaTory myopathies study is a prospective diagnostic accuracy study with an over-complete study design. 100 patients suspected of an IIM excluding IBM will be included. A reference diagnosis will be assigned by an expert panel using all clinical information and all results of all ancillary tests available, including 6 months of follow-up. Several predefined diagnostic strategies will be compared against the reference diagnosis to find the optimal diagnostic strategy. ETHICS AND DISSEMINATION: Ethical approval was obtained from the medical ethics committee of the Academic Medical Centre, University of Amsterdam, The Netherlands (2019-814). The results will be distributed through conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: Netherlands trial register; NL8764.

Patient Satisfaction With the Head and Neck Cancer Telephone Triage Service During the COVID-19 Pandemic.

Background A telephone triage consultation, as part of the two-week wait head and neck cancer referral pathway, was implemented nationally in March 2020. This was in response to the COVID-19 pandemic to stream cancer referrals to minimize unnecessary interactions and appointments with health services. The aim of this study is to assess patient satisfaction with this novel telephone triage system in the setting of a district general hospital. Methods A custom designed patient satisfaction questionnaire covering different facets of the patient experience was used. These questions were adapted from several internally validated questionnaires. A retrospective telephone survey was conducted by interviewers for all continuous new head and neck cancer referrals over two 4-week periods in 2020. Questionnaire responses to the initial modality of consult (either telephone triage or face to face) were collected, and data were analysed both qualitatively and quantitatively. Results Seventy-five responses were received, with 51 patients providing feedback on an initial telephone triage consultation. Patients rated the telephone triage consultation to be between satisfied and very satisfied across most domains, with an overall score of 4.29 out of 5. Accessibility and efficiency of the telephone triage were the domains with the least satisfaction. Fifty-five percent of patients would be happy to receive a similar telephone triage consultation beyond the pandemic. Qualitative analysis showed praise for the safety and convenience of the telephone triage consultation during the pandemic but highlighted a general preference for a face-to-face consultation and dissatisfaction regarding a lack of physical examination. Conclusions Overall, patients are satisfied with the telephone triage consultation employed in the pandemic, with high satisfaction rates for multiple aspects of care. However, there were concerns regarding the accessibility and inefficiency associated with a lack of/delayed physical examination and inability to adequately address the fear and anxiety associated with the referral. A mixed response is obtained on whether the telephone triage system should stay for the long run.

The Impact of the Auckland Cellulitis Pathway on Length of Hospital Stay, Mortality Readmission Rate, and Antibiotic Stewardship.

BACKGROUND: The Dundee classification of cellulitis severity, previously shown to predict disease outcomes, provides an opportunity to improve the management of patients with cellulitis. METHODS: We developed and implemented a pathway to guide the management of adults with cellulitis based on their Dundee severity class, and measured its effect on patient outcomes. We compared the outcomes in patients admitted to Auckland City Hospital (ACH) between July 2014 and July 2015 (the baseline cohort) with those in patients admitted between June 2017 and June 2018 (the intervention cohort). RESULTS: The median length of stay was shorter in the intervention cohort (0.7 days, interquartile range (IQR) 0.1 to 3.0 days) than in the baseline cohort (1.8 days, IQR 0.1 to 4.4 days; P < .001). The 30-day mortality rate declined from 1.8% (19/1092) in the baseline cohort to 0.7% (10/1362; P = .02) in the intervention cohort. The 30-day cellulitis readmission rate increased from 6% in the baseline cohort to 11% (P < .001) in the intervention cohort. Adherence to the ACH cellulitis antibiotic guideline improved from 38% to 48% (P < .01) and was independently associated with reduced length of stay. CONCLUSIONS: The implementation of the Auckland cellulitis pathway, readily generalizable to other settings, improved the outcomes in patients with cellulitis, and resulted in an annual saving of approximately 1000 bed days.

Testing a gamified Spider App to reduce spider fear and avoidance.

Mobile applications are increasingly part of mental health programs and various apps have been developed for treating anxiety disorders. Typically, they aim to improve anxiety symptoms via established CBT techniques, such as exposure principles, which are considered extremely unpleasant for fearful individuals. We combined in a mobile application exposure principles with gamification elements (e.g. narrative background, level progression, points, and feedback). These elements should increase the motivation for confronting spider images and decrease the experienced distress. To evaluate the application, two groups of spider-fearful individuals played either the Spider App (experimental group) or a non-spider associated app (control group) twice a day for approximately 12 min for 7 days. After this week, participants of the experimental group showed less avoidance behavior of spiders (BAT), as well as lower anxiety of spiders (SPQ, FAS). Groups were not different in measures of depression or psychological distress. Interestingly, participants playing the Spider App reported higher anxiety, disgust and arousal ratings shortly after playing the app. However, anxiety, disgust, and arousal ratings decreased from day to day. We discuss our findings with respect to implications for the clinical practice.

Are You There? Genetic Variation Impacts Long-Distance Connections in Diabetes.

A new study by Fasolino et al. defines how genetic variation in a mouse model of type 1 diabetes mellitus (T1DM) affects long-distance genomic interactions. The research has widespread implications for understanding how genetic diversity impacts disease susceptibility, and raises important concepts about mechanisms that can be influenced by genetic diversity between individuals.

The Role of Visual Feedback about Motion of the Ground on Postural Sway.

We asked whether body sway would be influenced by visual information about motion of the ground surface. On a ship at sea, standing participants performed a demanding visual search task or a simple visual inspection task. Display content was stationary relative to the ship or relative to the Earth. Participants faced the ship's bow or its port side. Performance on the visual search task was representative of terrestrial studies. Body sway was greater during viewing of the Earth Stationary displays than during viewing of the Ship Stationary displays. We discuss possible implications of these results for theoretical and applied issues.

Sensitivity to changes in dynamic affordances for walking on land and at sea.

We investigated the perception of affordances for walking along a narrow path. We asked whether participants could perceive changes in affordances brought about by manipulation of properties of the body, or of the environment, without direct practice of the to-be-perceived affordance, and without external feedback about the accuracy of perception. In Experiment 1, participants made a series of 8 judgments of how far they could walk along a narrow path either, 1) without added weight, 2) while wearing a weighted vest, or 3) while wearing weights on their ankles. Before walking, mean judgments were lower when wearing weights than in the no-weight condition. In addition, in both weight conditions judgments changed across the series of 8 judgments, in the direction of greater accuracy. Control of the body in walking also can be influenced by motion of the ground surface, as commonly happens in vehicles. In Experiment 2, on a ship at sea, we evaluated the effects of walking with or without weight added to the body at the ankles. We again asked participants (experienced maritime crewmembers) to judge how far they could walk along a narrow path, with versus without ankle weights. As in Experiment 1, judgments made before walking mirrored the observed differences in walking performance. In addition, we again found evidence that judgment improved (without walking practice, or feedback) over the series of judgments. We conclude that participants were sensitive to (and spontaneously learned about) how affordances for walking were influenced by changes in the dynamics of body and the environment.

Unstable coupling of body sway with imposed motion precedes visually induced motion sickness.

Motion sickness is preceded by differences in the quantitative kinematics of body sway between individuals who (later) become sick and those who do not. In existing research, this effect has been demonstrated only in measures of body sway, relative to the earth. However, body sway can become coupled with imposed oscillatory motion of the illuminated environment, and the nature of this coupling may differ between individuals who become sick and those who do not. We asked whether body sway would become coupled to complex oscillations of the illuminated environment, and whether individual differences in such coupling might be precursors of motion sickness. Standing participants (women) were exposed to complex oscillation of the illuminated environment. We examined the strength of coupling as a function of time during exposure. Following exposure, some participants reported motion sickness. The nature and temporal evolution of coupling differed between participants who later reported motion sickness and those who did not. Our results show that people can couple the complex dynamics of body sway with complex imposed motion, and that differences in the nature of this coupling are related to the risk of motion sickness.

Adaptive perception of changes in affordances for walking on a ship at sea.

Ocean waves cause oscillatory motion of ships. Oscillatory ship motion typically is greater in roll (i.e., the ship rolling from side to side) than in pitch (i.e., tipping from front to back). Affordances for walking on a ship at sea should be differentially influenced by ship motion in roll and pitch. When roll exceeds pitch, the maximum walkable distance within a defined path should be greater when walking along the ship's short, or athwart axis than when walking along its long, or fore-aft axis. When pitch exceeds roll, this relation should be reversed. We asked whether such changes in ship motion would be reflected in judgments of direction-specific affordances for walking. Participants (experienced maritime crewmembers) judged how far they could walk along a narrow path on the ship deck. On different days, sailing conditions were such that the relative magnitude of pitch and roll was reversed. Judgments of direction-specific affordances for walking mirrored these changes in ship motion. The accuracy of judgments was consistent across directions, and across changes in ship motion. We conclude that experienced maritime crewmembers were sensitive to dynamic variations in affordances for walking that were, themselves, a function of dynamic properties of the animal-environment system.

Impact of pulsed UV-B stress exposure on plant performance: How recovery periods stimulate secondary metabolism while reducing adaptive growth attenuation.

Upon continuous stress exposure, plants display attenuated metabolic stress responses due to regulatory feedback loops. Here, we have tested the hypothesis that pulsed stress exposure with intervening recovery periods should affect these feedback loops, thereby causing increased accumulation of stress-induced metabolites. The response of Arabidopsis plantlets to continuous UV-B exposure (Cuv ) was compared with that of pulsed UV-B exposure (Puv ). The differential responses to Puv versus Cuv were monitored at the level of gene expression and metabolite accumulation, using wild type (WT) and different mutant lines. In comparison with Cuv , Puv increased sinapyl and flavonol (S + F) content, whereas adaptive growth attenuation was reduced. Furthermore, in a myb4 mutant (AtMYB4, repressor-type R2R3-MYB transcription factor), the S + F content was increased only for Cuv , but not beyond the level for Puv observed in WT. These observations and the ability of AtMYB4 to repress AtMYB12/AtMYB111-mediated activation of target gene promoters (pCHS and pFLS) indicate that the increase of S + F content after Puv observed in WT plants results from reduced feedback inhibition by AtMYB4. The results support the notion that stress-induced metabolic changes not necessarily cause a growth penalty. Furthermore, the observed Puv -induced increase in flavonol accumulation may stimulate reevaluation of commercial plant production practices.

Association of the Dundee severity classification with mortality, length of stay and readmission in adult inpatients with cellulitis.

Background: The Dundee classification is a simple severity assessment tool that could optimize treatment decisions and clinical outcomes in adult patients with cellulitis; however, it has not been validated in a large cohort. Objectives: To determine whether the Dundee classification reliably identified those patients with cellulitis who had a higher mortality, a longer length of hospital stay or an increased risk of readmission. Methods: We performed a retrospective study of all adults with a primary discharge diagnosis of cellulitis admitted to Auckland City Hospital from August 2013 to June 2015. We classified patients by severity using the Dundee scoring system. Results: The 30 day all-cause mortality in adult patients with a discharge diagnosis of cellulitis was 2% (29/1462) overall, and was 1% (10/806), 2% (6/271), 3% (10/353) and 9% (3/32) in Classes 1, 2, 3 and 4 of the Dundee classification, respectively (P = 0.01). Mortality was strongly associated with age >65 years (OR 9.37, 95% CI 3.00-41.23) and with heart failure (OR 6.16, 95% CI 2.73-14.23). There were significant associations between the Dundee classification and the incidence of bacteraemia, the length of hospital stay and the rate of readmission to hospital. Conclusions: The Dundee classification is a simple, reliable tool that can be easily applied in clinical settings to predict risk of mortality in order to determine which patients can be managed in the community with oral or intravenous therapy, and which require inpatient care.

Real-time visual feedback about postural activity increases postural instability and visually induced motion sickness.

BACKGROUND: Several studies have shown that the kinematics of standing body sway can be influenced by the provision of real time feedback about postural activity through visual displays. RESEARCH QUESTION: We asked whether real time visual feedback about the position of the body's center of pressure (COP) might affect body sway and the occurrence of visually induced motion sickness. METHODS: Standing participants (women) were exposed to complex visual oscillation in a moving room, a device that nearly filled the field of view. During exposure to complex visual oscillations, we provided real time feedback about displacements of the body's center of pressure through a visual display presented on a tablet computer. RESULTS: The incidence of motion sickness was greater than in a closely related study that did not provide real time feedback. We monitored the kinematics of the body's center of pressure before and during exposure to visual motion stimuli. Body sway differed between participants who reported motion sickness and those who did not. These differences existed before any participants experienced subjective symptoms of motion sickness. SIGNIFICANCE: Real time visual feedback about COP displacement did not reduce visually induced motion sickness, and may have increased it. We identified postural precursors of motion sickness that may have been exacerbated by the COP display. The results indicate that visual feedback about postural activity can destabilize postural control, leading to negative side effects. We suggest possible alternative types of visual displays that might help to stabilize posture, and reduce motion sickness.

Postural time-to-contact as a precursor of visually induced motion sickness.

The postural instability theory of motion sickness predicts that subjective symptoms of motion sickness will be preceded by unstable control of posture. In previous studies, this prediction has been confirmed with measures of the spatial magnitude and the temporal dynamics of postural activity. In the present study, we examine whether precursors of visually induced motion sickness might exist in postural time-to-contact, a measure of postural activity that is related to the risk of falling. Standing participants were exposed to oscillating visual motion stimuli in a standard laboratory protocol. Both before and during exposure to visual motion stimuli, we monitored the kinematics of the body's center of pressure. We predicted that postural activity would differ between participants who reported motion sickness and those who did not, and that these differences would exist before participants experienced subjective symptoms of motion sickness. During exposure to visual motion stimuli, the multifractality of sway differed between the Well and Sick groups. Postural time-to-contact differed between the Well and Sick groups during exposure to visual motion stimuli, but also before exposure to any motion stimuli. The results provide a qualitatively new type of support for the postural instability theory of motion sickness.

The Role of Palliative Care in Chronic Progressive Neurological Diseases-A Survey Amongst Neurologists in the Netherlands.

Background: Chronic progressive neurological diseases like high grade glioma (HGG), Parkinson's disease (PD), and multiple sclerosis (MS) are incurable, and associated with increasing disability including cognitive impairment, and reduced life expectancy. Patients with these diseases have complex care needs. Therefore, timely advance care planning (ACP) is required. Our aim was to investigate timing and content of discussions on treatment restrictions, i.e., to initiate, withhold, or withdraw treatment in patients with HGG, PD, and MS, from the neurologists' perspective. Methods: We performed a national online survey amongst consultants in neurology and residents in The Netherlands. The questionnaire focused on their daily practice concerning timing and content of discussions on treatment restrictions with patients suffering from HGG, PD or MS. We also inquired about education and training in discussing these issues. Results: A total of 125 respondents [89 neurologists (71%), 62% male, with a median age of 44 years, and 36 residents (29%), 31% male with a median age of 29 years] responded. Initial discussions on treatment restrictions were said to take place during the first year after diagnosis in 28% of patients with HGG, and commonly no earlier than in the terminal phase in patients with PD and MS. In all conditions, significant cognitive decline was the most important trigger to advance discussions, followed by physical decline, and initiation of the terminal phase. Most discussed issues included ventilation, resuscitation, and admission to the intensive care unit. More than half of the consultants in neurology and residents felt that they needed (more) education and training in having discussions on treatment restrictions. Conclusion: In patients with HGG discussions on treatment restrictions are initiated earlier than in patients with PD or MS. However, in all three diseases these discussions usually take place when significant physical and cognitive decline has become apparent and commonly mark the initiation of end-of-life care. More than half of the responding consultants in neurology and residents feel the need for improvement of their skills in performing these discussions.