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Background: A pectoralis major (PM) transfer is a viable treatment option for patients with scapular winging due to long thoracic nerve (LTN) palsy not responding to nonsurgical management. However, the long-term outcomes remain unknown. Therefore, the purpose of this study was to evaluate the long-term outcome of shoulder function (ie, minimum follow-up of 10 years) and quality-of-life (QoL) of patients treated for scapular winging due to LTN palsy with a PM transfer. Methods: This observational cohort study included 15 patients (16 shoulders) who underwent PM transfer, using a tendoachilles allograft, between 1995 and 2012. Shoulder forward flexion and abduction were analyzed preoperatively, 1 year after surgery and at the final follow-up. SF-36 component scores (physical component summary (PCS) and mental component summary (MCS)) were used to evaluate the QoL. Results: Shoulder forward flexion and abduction measured in degrees improved from 86 (SD 14.5) and 82 (SD 33.8) preoperatively to 140 (SD 27.3) and 138 (31.3) at 1 year postoperatively. After a median follow-up of 17 years, mean shoulder functions were slightly lower than at 1 year postoperatively, but still better than preoperative function, ie, forward flexion 121 (SD 41.9) and abduction 122 (SD 44.5). The mean PCS score at the final follow-up was 41.9 (SD 9.7), and the mean MCS score was 49.9 (SD 12.5). Better shoulder function at the final follow-up was significantly associated with higher QoL in terms of PCS scores (P = .023), but not MCS scores (P = .287). Conclusion: The results of the present study indicate that PM transfer augmented with an achilles tendon allograft for scapular winging due to LTN palsy leads to functional improvements that persist in long term. These functional improvements likely translate to better QoL based on their association.

Abstract Objectives This study aimed to evaluate the potential clinical value of a new brain age prediction model as a single interpretable variable representing the condition of our brain. Among many clinical use cases, brain age could be a novel outcome measure to assess the preventive effect of life-style interventions. Methods The REMEMBER study population (N = 742) consisted of cognitively healthy (HC,N = 91), subjective cognitive decline (SCD,N = 65), mild cognitive impairment (MCI,N = 319) and AD dementia (ADD,N = 267) subjects. Automated brain volumetry of global, cortical, and subcortical brain structures computed by the CE-labeled and FDA-cleared software icobrain dm (dementia) was retrospectively extracted from T1-weighted MRI sequences that were acquired during clinical routine at participating memory clinics from the Belgian Dementia Council. The volumetric features, along with sex, were combined into a weighted sum using a linear model, and were used to predict ‘brain age’ and ‘brain predicted age difference’ (BPAD = brain age–chronological age) for every subject. Results MCI and ADD patients showed an increased brain age compared to their chronological age. Overall, brain age outperformed BPAD and chronological age in terms of classification accuracy across the AD spectrum. There was a weak-to-moderate correlation between total MMSE score and both brain age (r = -0.38,p

Abstract We delve into the human brain’s remarkable capacity for adaptability and sustained cognitive functioning, phenomena traditionally encompassed as executive functions or cognitive control. The neural underpinnings that enable the seamless navigation between transient thoughts without detracting from overarching goals form the core of our article. We discuss the concept of “metacontrol,” which builds upon conventional cognitive control theories by proposing a dynamic balancing of processes depending on situational demands. We critically discuss the role of oscillatory processes in electrophysiological activity at different scales and the importance of desynchronization and partial phase synchronization in supporting adaptive behavior including neural noise accounts, transient dynamics, phase-based measures (coordination dynamics) and neural mass modelling. The cognitive processes focused and neurophysiological avenues outlined are integral to understanding diverse psychiatric disorders thereby contributing to a more nuanced comprehension of cognitive control and its neural bases in both health and disease.

Abstract Introduction Neuromuscular diseases (NMDs) entail a group of mostly inherited genetic disorders with heterogeneous phenotypes impacting muscles, the central or peripheral nervous system. They can lead to severe disabilities and shortened lifespans. Despite their severity, NMDs often lack in public awareness and appropriate medical and social support. Telemedicine can improve patients’ and caregivers’ lives by enhancing continuity of and access to care. The first aim of this systematic review was to summarise the status quo of telemedicine services for patients with NMDs. Secondly, barriers and facilitators of the respective implementation processes should be analysed. Methods The databases PubMed, Web of Science and CENTRAL by Cochrane were searched in May 2022. To be truly explorative, any original evidence from any setting was included. Two independent researchers completed the screening process. Data was extracted and analysed using the taxonomy of Bashshur et al. (2011) and the Consolidated Framework for Implementation Research (CFIR). Results Fifty-seven original papers were included in the systematic review. The results showed a high representation of teleconsultations and remote monitoring studies. Teleconsultations replaced in person appointments and telemonitoring mostly focused on ventilation. Physical therapy, pulmonology, neurology, and psychology were the most represented medical specialties. We found barriers and facilitators relating to implementation mainly referred to the intervention and the individuals involved. Technical errors and inaccessibility due to a lack of technical devices or the patient’s disability were stated as hindrances. A positive mindset of users as well as patient empowerment were necessary for the adoption of new technology. Technophobia or uncertainty around technology negatively impacted the implementation process. Discussion This systematic review provides an overview of the current use of telemedicine in patients with NMDs. The distribution of telemedicine interventions between the defined domains was very heterogenous. Previous research has neglected to fully describe the implementation process of telemedicine for NMDs. Conclusion The evidence shows that telemedicine can benefit patients with NMDs in a multitude of ways. Therefore, health policies should endorse and incentivise the uptake of telemedicine by institutions and health care workers. Further research needs to be conducted to confirm the current evidence and close existing research gaps.

BackgroundIn schizophrenia patients, spontaneous speech production has been hypothesized as correlating with right hemispheric activation, including the inferior frontal and superior temporal gyri as speech-relevant areas. However, robust evidence for this association is still missing. The aim of the present fMRI study is to examine BOLD signal changes during natural, fluent speech production in patients with schizophrenia in the chronic phase of their disease.MethodsUsing a case–control design, the study included 15 right-handed patients with schizophrenia spectrum disorders as well as 15 healthy controls. The participants described eight pictures from the Thematic Apperception Test for 1 min each, while BOLD signal changes were measured with 3T fMRI. The occurrence of positive and negative formal thought disorders was determined using standardized psychopathological assessments.ResultsWe found significant BOLD signal changes during spontaneous speech production in schizophrenia patients compared to healthy controls, particularly in the right hemispheric network. A post-hoc analysis showed that this right-hemispheric lateralization was mainly driven by activation during experimental rests. Furthermore, the TLI sum value in patients correlated negatively with BOLD signal changes in the right Rolandic operculum.ConclusionsPossible underlying factors for this inverse right-hemispheric lateralization of speech-associated areas are structural changes and transmitter system alterations, as well as a lack of neural downregulation in schizophrenia patients during rest periods due to dysfunctional executive functions. When examining spontaneous speech as the most natural form of language, other influencing factors, such as social cognition or emotional processing, should be considered. Our results indicate that future studies should consider group differences during rest, which might provide additional information typically covered in differential contrasts.

IntroductionChanges in brain structure and function occur with aging. However, there is substantial heterogeneity both in terms of when these changes begin, and the rate at which they progress. Understanding the mechanisms and/or behaviors underlying this heterogeneity may allow us to act to target and slow negative changes associated with aging.MethodsUsing T1 weighted MRI images, we applied a novel algorithm to determine the physiological age of the brain (brain-predicted age) and the predicted age difference between this physiologically based estimate and chronological age (BrainPAD) to 551 sedentary adults aged 65 to 84 with self-reported cognitive complaint measured at baseline as part of a larger study. We also assessed maximal aerobic capacity with a graded exercise test, physical activity and sleep with accelerometers, and body composition with dual energy x-ray absorptiometry. Associations were explored both linearly and logistically using categorical groupings.ResultsVisceral Adipose Tissue (VAT), Total Sleep Time (TST) and maximal aerobic capacity all showed significant associations with BrainPAD. Greater VAT was associated with higher (i.e,. older than chronological) BrainPAD (r = 0.149 p = 0.001)Greater TST was associated with higher BrainPAD (r = 0.087 p = 0.042) and greater aerobic capacity was associated with lower BrainPAD (r = - 0.088 p = 0.040). With linear regression, both VAT and TST remained significant (p = 0.036 and 0.008 respectively). Each kg of VAT predicted a 0.741 year increase in BrainPAD, and each hour of increased TST predicted a 0.735 year increase in BrainPAD. Maximal aerobic capacity did not retain statistical significance in fully adjusted linear models.DiscussionAccumulation of visceral adipose tissue and greater total sleep time, but not aerobic capacity, total daily physical activity, or sleep quantity and/or quality are associated with brains that are physiologically older than would be expected based upon chronological age alone (BrainPAD).

Abstract Background Epileptic seizures are an established comorbidity of Alzheimer’s disease (AD). Subclinical epileptiform activity (SEA) as detected by 24-h electroencephalography (EEG) or magneto-encephalography (MEG) has been reported in temporal regions of clinically diagnosed AD patients. Although epileptic activity in AD probably arises in the mesial temporal lobe, electrical activity within this region might not propagate to EEG scalp electrodes and could remain undetected by standard EEG. However, SEA might lead to faster cognitive decline in AD. Aims 1. To estimate the prevalence of SEA and interictal epileptic discharges (IEDs) in a well-defined cohort of participants belonging to the AD continuum, including preclinical AD subjects, as compared with cognitively healthy controls. 2. To evaluate whether long-term-EEG (LTM-EEG), high-density-EEG (hd-EEG) or MEG is superior to detect SEA in AD. 3. To characterise AD patients with SEA based on clinical, neuropsychological and neuroimaging parameters. Methods Subjects (n = 49) belonging to the AD continuum were diagnosed according to the 2011 NIA-AA research criteria, with a high likelihood of underlying AD pathophysiology. Healthy volunteers (n = 24) scored normal on neuropsychological testing and were amyloid negative. None of the participants experienced a seizure before. Subjects underwent LTM-EEG and/or 50-min MEG and/or 50-min hd-EEG to detect IEDs. Results We found an increased prevalence of SEA in AD subjects (31%) as compared to controls (8%) (p = 0.041; Fisher’s exact test), with increasing prevalence over the disease course (50% in dementia, 27% in MCI and 25% in preclinical AD). Although MEG (25%) did not withhold a higher prevalence of SEA in AD as compared to LTM-EEG (19%) and hd-EEG (19%), MEG was significantly superior to detect spikes per 50 min (p = 0.002; Kruskall–Wallis test). AD patients with SEA scored worse on the RBANS visuospatial and attention subset (p = 0.009 and p = 0.05, respectively; Mann–Whitney U test) and had higher left frontal, (left) temporal and (left and right) entorhinal cortex volumes than those without. Conclusion We confirmed that SEA is increased in the AD continuum as compared to controls, with increasing prevalence with AD disease stage. In AD patients, SEA is associated with more severe visuospatial and attention deficits and with increased left frontal, (left) temporal and entorhinal cortex volumes. Trial registration Clinicaltrials.gov, NCT04131491. 12/02/2020.

Background Withdrawal of reimbursement for low-value care through a policy change, ie, active disinvestment, is considered a potentially effective de-implementation strategy. However, previous studies have shown conflicting results and the mechanism through which active disinvestment may be effective is unclear. This study explored how the active disinvestment initiative regarding subacromial decompression (SAD) surgery for subacromial pain syndrome (SAPS) in the Netherlands influenced clinical decision-making around surgery, including the perspectives of orthopedic surgeonsand hospital sales managers.Methods We performed 20 semi-structured interviews from November 2020 to October 2021 with ten hospital sales managers and ten orthopedic surgeons from twelve hospitals across the Netherlands as relevant stakeholders in the active disinvestment process. The interviews were video-recorded and transcribed verbatim. Inductive thematic analysis was used to analyse interview transcripts independently by two authors and discrepancies were resolved through discussion.Results Two overarching themes were identified that negatively influenced the effect of the active disinvestment initiative for SAPS. The first theme was that the active disinvestment represented a “Too small piece of the pie” indicating little financial consequences for the hospital as it was merely used in negotiations with healthcare insurers to reduce costs, required a disproportionate amount of effort from hospital staff given the small saving-potential, and was not clearly defined nor enforced in the overall healthcare insurer agreements. The second theme was “They [healthcare insurer] got it wrong,” as the evidence and guidelines had been incorrectly interpreted, the active disinvestment was at odds with clinician experiences and beliefs and was perceived as a reduction in their professional autonomy.Conclusion The two overarching themes and their underlying factors highlight the complexity for active disinvestment initiatives to be effective. Future de-implementation initiatives including active disinvestment should engage relevant stakeholders at an early stage to incorporate their different perspectives, gain support and increase the probability of success.

Abstract The brain dynamics underlying working memory (WM) unroll via transient frequency-specific large-scale brain networks. This multidimensionality (time, space, and frequency) challenges traditional analyses. Through an unsupervised technique, the time delay embedded-hidden Markov model (TDE-HMM), we pursue a functional network analysis of magnetoencephalographic data from 38 healthy subjects acquired during an n-back task. Here we show that this model inferred task-specific networks with unique temporal (activation), spectral (phase-coupling connections), and spatial (power spectral density distribution) profiles. A theta frontoparietal network exerts attentional control and encodes the stimulus, an alpha temporo-occipital network rehearses the verbal information, and a broad-band frontoparietal network with a P300-like temporal profile leads the retrieval process and motor response. Therefore, this work provides a unified and integrated description of the multidimensional working memory dynamics that can be interpreted within the neuropsychological multi-component model of WM, improving the overall neurophysiological and neuropsychological comprehension of WM functioning.

Abstract Background Inclusion body myositis (IBM) is the most frequent type of myositis in elder patients with a slow chronic progression and refractory to treatment. Previous cost of illness (COI) studies in IBM used claims data to estimate direct costs in the US. No evidence exists globally on both direct and indirect costs in IBM from a societal perspective. We conducted a survey in patients registered in the German IBM patient registry. Self-developed items were used to assess the utilized healthcare resources and estimate the cost. The German Self-Administered Comorbidity Questionnaire (SCQ-D), the sIBM Physical Functioning Assessment (sIFA) and patient-reported measures for satisfaction and improvements in healthcare were applied for an explorative analysis. Results In total, 82 patients completed the survey. We estimated the mean total annual per capita COI of US$102,682 (95% CI US$82,763–US$123,090) in 2021. 92.7% of the total COI were direct costs. Medical costs were similar to nonmedical costs, with substantial costs for pharmacotherapy and informal care. Depending on the prevalence estimate, the total national COI per year were US$42.7 million–US$213.7 million. Significant differences in total COI were identified for the degree of disability, marital and employment status (p

Abstract Background To understand the health-related quality of life (HRQoL) in inclusion body myositis (IBM) from a holistic perspective on the background of a complex care situation. The focus was on how the patient journey may be structured over the course of this rare disease. Methods An exploratory qualitative study was performed via in-depth semi-structured interviews. Seven patients (males n = 5) with 2011 European Neuromuscular Centre (ENMC) IBM criteria from the German IBM patient registry were interviewed for this study. The dynamic network approach of resilience and the throughput-model of health services research were used to structure the qualitative analysis. Results Our results suggest that IBM patients experience the holistic HRQoL and care situation typically in four phases: (1) uncertainty about physical vulnerability until diagnosis, (2) promising treatment approaches, (3) self-management and dyadic coping, (4) weak body, busy mind and caregiver burden. The homophonous in-vivo code “patience journey” describes the frequently reported emotional perspective of the patient journey. Although the overarching theme of perceived social support varied throughout these phases, a reliable patient-partner-dyad may lead to improved HRQoL in the long-term. Conclusions New hypotheses for future quantitative research were generated to better understand the IBM patients’ burden in the long term. The identified relevance of social support emphasizes the patients’ need to handle IBM as manageable in medical settings. During exhausting phases of IBM progression, more effective care elements for patients and their partners could disclose varying needs. Strengthening multi-professional healthcare services via individualised informational, practical, or emotional support could improve HRQoL, especially since there is no curative treatment available so far.

Abstract We explore the possibility of embedding thermal leptogenesis within a first-order phase transition (FOPT) such that RHNs remain massless until a FOPT arises. Their sudden and violent mass gain allows the neutrinos to become thermally decoupled, and the lepton asymmetry generated from their decay can be, in principle, free from the strong wash-out processes that conventional leptogenesis scenarios suffer from, albeit at the cost of new washout channels. To quantify the effect of this enhancement, we consider a simple setup of a classically scale-invariant B − L potential, which requires three RHNs with similar mass scales, in the “strong-washout” regime of thermal leptogenesis. Here we find that parameter space which requires M N ~ 1011 GeV without bubble assistance is now predicted at M N ~ 5 × 109 GeV suggesting a sizeable reduction from bubble effects. We numerically quantify to what extent such a framework can alleviate strong-washout effects and we find the lower bound on the RHN mass, M N ~ 107 GeV, below which bubble-assisted leptogenesis cannot provide an enhancement. We also study the signature possibly observable at GW terrestrial interferometers and conclude that bubble-assisted leptogenesis models with relatively light masses, M N ≲ 5 × 109 GeV may be probable.

Abstract COVID-19 can induce neurological sequelae, negatively affecting the quality of life. Unravelling this illness's impact on structural brain connectivity, white-matter microstructure (WMM), and cognitive performance may help elucidate its implications. This cross-sectional study aimed to investigate differences in these factors between former hospitalised COVID-19 patients (COV) and healthy controls. Group differences in structural brain connectivity were explored using Welch-two sample t-tests and two-sample Mann–Whitney U tests. Multivariate linear models were constructed (one per region) to examine fixel-based group differences. Differences in cognitive performance between groups were investigated using Wilcoxon Rank Sum tests. Possible effects of bundle-specific FD measures on cognitive performance were explored using a two-group path model. No differences in whole-brain structural organisation were found. Bundle-specific metrics showed reduced fiber density (p = 0.012, Hedges’ g = 0.884) and fiber density cross-section (p = 0.007, Hedges’ g = 0.945) in the motor segment of the corpus callosum in COV compared to healthy controls. Cognitive performance on the motor praxis and digit symbol substitution tests was worse in COV than healthy controls (p

Purpose: To provide further insight into the variation in decision making to perform subacromial decompression (SAD) surgery in patients with subacromial pain syndrome (SAPS) and its influencing factors. Methods: Between November 2021 and February 2022, we invited 202 Dutch Shoulder and Elbow Society members to participate in a cross-sectional Web-based survey including 4 clinical scenarios of SAPS patients. Scenarios varied in patient characteristics, clinical presentation, and other contextual factors. For each scenario, respondents were asked (1) to indicate whether they would perform SAD surgery, (2) to indicate the probability of benefit of SAD surgery (i.e., pain reduction), (3) to indicate the probability of harm (i.e., complications), and (4) to rank the 5 most important factors influencing their treatment decision. Results: A total of 78 respondents (39%) participated. The percentage of respondents who would perform SAD surgery ranged from 4% to 25% among scenarios. The median probability of perceived benefit ranged between 70% and 79% across scenarios for respondents indicating to perform surgery compared with 15% to 29% for those indicating not to perform surgery. The difference in the median probability of perceived harm ranged from 3% to 9% for those indicating to perform surgery compared with 8% to 13% for those indicating not to perform surgery. Surgeons who would perform surgery mainly reported patient-related factors (e.g., complaint duration and response to physical therapy) as the most important factors to perform SAD surgery, whereas surgeons who would not perform surgery mainly reported guideline-related factors. Conclusions: Overall, Dutch orthopaedic shoulder surgeons are reluctant to perform SAD surgery in SAPS patients. There is substantial variation among orthopaedic surgeons regarding decisions to perform SAD surgery for SAPS even when evaluating identical scenarios, where particularly the perceived benefit of surgery differed between those who would perform surgery and those who would not. Surgeons who would not perform SAD surgery mainly referred to guideline-related factors as influential factors for their decision, whereas those who would perform SAD surgery considered patient-related factors more important. Clinical Relevance: There is substantial variation in decision making to perform SAD surgery for SAPS between individual orthopaedic surgeons for identical case scenarios.

ABSTRACTPredicting the long-term outcome of multiple sclerosis (MS) remains an important challenge to this day. As the gut microbiota is emerging as a potential player in MS, we investigated in this study whether gut microbial composition at baseline is related to long-term disability worsening in a longitudinal cohort of 111 MS patients. Fecal samples and extensive host metadata were collected at baseline and 3 months post-baseline, with additional repeated neurological measurements performed over (median) 4.4 y. Worsening (with EDSS-Plus) occurred in 39/95 patients (outcome undetermined for 16 individuals). The inflammation-associated, dysbiotic Bacteroides 2 enterotype (Bact2) was detected at baseline in 43.6% of worsened patients, while only 16.1% of non-worsened patients harbored Bact2. This association was independent of identified confounders, and Bact2 was more strongly associated with EDSS-Plus than neurofilament light chain (NfL) plasma levels. Furthermore, using fecal sampling performed 3 months post-baseline, we observed Bact2 to be relatively stable, suggesting its potential use as a prognostic biomarker in MS clinical practice.

Abstract Background Sarcopenia is highly prevalent in haemodialysis (HD) patients and linked to a poor prognosis regarding comorbidities and premature mortality. Previous studies assessed the effects of neuromuscular electrical stimulation in haemodialysis patients. This study adds to the relevance of neuromuscular electrical stimulation (NMES) applications combined with a virtual reality (VR) distraction to increase intensity, dosage, and efficiency of NMES and slow sarcopenia progression in HD patients. Methods We conducted a 12-week multicenter prospective randomised controlled trial. The patients were randomly assigned to one of the three groups: neuromuscular electrical stimulation with or without combined virtual reality distraction or control group. Results The final analysis included 32 haemodialysis patients (mean age of 68 ± 10 years, 26 men). Interaction effects between groups and time (12 weeks) were significant regarding serum albumin levels (p = 0.008) and left quadriceps femoris muscle (QFM) force (p = 0.026). Both endpoints were increased in the NMES compared to the CO group at the end of the intervention. The NMES group increased serum albumin levels significantly after 12 weeks. The main effect of time was an increase in mean right QFM force between beginning and end of the intervention (p = 0.021). Functional capacity improved after 12 weeks in the NMES and NMES + VR but not in the control group, with a significant difference between the three groups (p = 0.022). Weight and body mass index increased in the NMES and NMES + VR groups, albeit not significantly. The effects of VR distraction on NMES efficiency were inconclusive. Conclusion Intradialytic NMES increases serum albumin level, functional capacity, muscle strength in lower limb and in tendency weight and body mass index of HD patients. Effects on VR distraction are inconclusive. Large-scaled follow-up studies on integrated sports programs with NMES and active training in combination with VR as distraction and motivation accelerator are needed. Trial registration German Clinical Trial Register: DRKS00029276 (Retrospectively registered: 30/06/2022).

Abstract Aims To evaluate the extent to which publication of high-quality randomised controlled trials(RCTs) in 2018 was associated with a change in volume or trend of subacromial decompression(SAD) surgery in patients with subacromial pain syndrome(SAPS) treated in hospitals across various countries. Methods Routinely collected administrative data of the Global Health Data@work collaborative were used to identify SAPS patients who underwent SAD surgery in six hospitals from five countries (Australia, Belgium, Netherlands, United Kingdom, United States) between 01/2016 and 02/2020. Following a controlled interrupted time series design, segmented Poisson regression was used to compare trends in monthly SAD surgeries before(01/2016-01/2018) and after(02/2018-02/2020) publication of the RCTs. The control group consisted of musculoskeletal patients undergoing other procedures. Results A total of 3.046 SAD surgeries were performed among SAPS patients treated in five hospitals; one hospital did not perform any SAD surgeries. Overall, publication of trial results was associated with a significant reduction in the trend to use SAD surgery of 2% per month (Incidence rate ratio (IRR) 0.984[0.971–0.998]; P = 0.021), but with large variation between hospitals. No changes in the control group were observed. However, publication of trial results was also associated with a 2% monthly increased trend (IRR 1.019[1.004–1.034]; P = 0.014) towards other procedures performed in SAPS patients. Conclusion Publication of RCT results was associated with a significantly decreased trend in SAD surgery for SAPS patients, although large variation between participating hospitals existed and a possible shift in coding practices cannot be ruled out. This highlights the complexities of implementing recommendations to change routine clinical practice even if based on high-quality evidence.

Along the pathway from behavioral symptoms to the development of psychotic disorders sits the multivariate mediating brain. The functional organization and structural topography of large-scale multivariate neural mediators among patients with brain disorders, however, are not well understood. Here, we design a high-dimensional brain-wide functional mediation framework to investigate brain regions that intermediate between baseline behavioral symptoms and future conversion to full psychosis among individuals at clinical high risk (CHR). Using resting-state functional magnetic resonance imaging (fMRI) data from 263 CHR subjects, we extract an α brain atlas and a β brain atlas: the former underlines brain areas associated with prodromal symptoms and the latter highlights brain areas associated with disease onset. In parallel, we identify and separate mediators that potentially positively and negatively mediate symptoms and psychosis, respectively, and quantify the effect of each neural mediator on disease development. Taken together, these results paint a brain-wide picture of neural markers that are potentially mediating behavioral symptoms and the development of psychotic disorders; additionally, they underscore a statistical framework that is useful to uncover large-scale intermediating variables in a regulatory biological system.

This study investigates the pilot-scale ozone treatment of reverse osmosis concentrate (ROC), originating from variable tank truck cleaning wastewater. The influence of ozonation on short- and long-term biodegradation potential was examined through respirometry and Zahn–Wellens, respectively. Ecotoxicity was also examined for several concentrate batches and ozonation steps. Chemical oxidation through ozone had a beneficial effect on chemical oxygen demand removal, with a removal efficiency up to 56%. Formation of short-term biochemical oxygen demand (BODst) was induced for several, but not all batches, showing the potential of subsequent biological treatment of ozonated ROC. An increase in the inherent biodegradability through Zahn-Wellens was observed for all tested samples after ozonation, rising to a maximum of 68% after 3 hours of ozonation, highlighting the importance of sludge adaptation. Ecotoxicity, tested with Artemia franciscana and the saltwater algae P. tricornutum, showed initial decreases in algae inhibition after short ozonation periods. An increase in algae inhibition was, however, seen after prolonged ozonation for all tested ROC samples, pointing to the formation of ecotoxic by-products. Artemia showed no significant toxicity effects. When applying biological treatment through Zahn-Wellens, a decrease in ecotoxicity was observed for several samples, likely through biological oxidation of the produced degradation products. HIGHLIGHTS Ozone removed recalcitrant COD from tank truck cleaning reverse osmosis concentrate.; Short-term and inherent biodegradability increased after extended ozone treatment.; Ecotoxicity showed initial decrease after ozone, but increased with extended treatment.; Biological post-treatment was seen as a good way to remove ecotoxic by-products.;

Abstract Advanced structural brain imaging techniques, such as diffusion tensor imaging (DTI), have been used to study the relationship between DTI-parameters and cognitive scores in multiple sclerosis (MS). In this study, we assessed cognitive function in 61 individuals with MS and a control group of 35 healthy individuals with the Symbol Digit Modalities Test, the California Verbal Learning Test-II, the Brief Visuospatial Memory Test-Revised, the Controlled Oral Word Association Test, and Stroop-test. We also acquired diffusion-weighted images (b = 1000; 32 directions), which were processed to obtain the following DTI scalars: fractional anisotropy, mean, axial, and radial diffusivity. The relation between DTI scalars and cognitive parameters was assessed through permutations. Although fractional anisotropy and axial diffusivity did not correlate with any of the cognitive tests, mean and radial diffusivity were negatively correlated with all of these tests. However, this effect was not specific to any specific white matter tract or cognitive test and demonstrated a general effect with only low to moderate individual voxel-based correlations of

Die digitale Transformation in der Medizin versetzt uns in die Lage, immer größere und komplexere Datenmengen in verwertbares Wissen zu verwandeln. Die klassische medizinische Evidenzgenerierung wird dadurch zunehmend ergänzt oder sogar teilweise ersetzt durch versorgungsnahe Daten bzw. Real-World-Data (RWD). Damit einher geht die Chance, Arzneimittelforschung besser, effizienter, sicherer und schneller zu gestalten. Erkenntnisse können schneller in die Versorgung und klinische Entscheidungsprozesse einfließen. Um diese Chance zu nutzen, gilt es, Althergebrachtes allmählich loszulassen.

Abstract Background The management of cognitive impairment is an important goal in the treatment of multiple sclerosis (MS). While cognitive rehabilitation has been proven to be effective in improving cognitive performance in MS, research in the elderly indicates a higher effectiveness of combined cognitive-motor rehabilitation. Here, we present the protocol of a randomised controlled clinical trial to assess whether a combined cognitive-motor telerehabilitation programme is more effective in improving working memory than only cognitive or motor training. Methods/design The CoMoTeMS-trial is a two-centre, randomised, controlled and blinded clinical trial. A total of 90 patients with MS will receive 12 weeks of either a combined cognitive-motor telerehabilitation programme or only cognitive or motor training. The primary outcome is a change in the digit span backwards. Secondary outcomes are other cognitive changes (Brief International Cognitive Assessment for Multiple Sclerosis and Backward Corsi), Expanded Disability Status Scale (EDSS), 6-Min Walk Test, 25-Foot Walk Test, 9-Hole Peg Test, anxiety and depression, fatigue, quality of life, cognitive and physical activity level, electroencephalography and magnetic resonance imaging of the brain. Discussion We hypothesise that the improvement in digit span backwards after 12 weeks of treatment will be significantly higher in the group treated with the combined cognitive-motor telerehabilitation programme, compared to the groups receiving only cognitive and only motor training. Trial registration ClinicalTrials.gov NCT05355389. Registered on 2 May 2022.

Abstract The patient-reported form of the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) assesses perceived problems attributable to cognitive and neuropsychiatric symptoms. It is inconsistently related to objective cognitive performance in multiple sclerosis (MS), while strongly correlated with depression. We assessed whether the relationship between subjective and objective cognitive screening tools is moderated by disability. Furthermore, we investigated the MSNQ as a screening tool for both cognitive impairment and depression. 275 MS patients completed the patient-reported MSNQ, two‐question screening tool for depression and Symbol Digit Modalities Test (SDMT) and were divided into Expanded Disability Status Scale (EDSS) subgroups: Low 0.0–3.0, Medium 3.5–6.0, High 6.5–9.0. MSNQ scores correlated significantly with depression but not SDMT in all subgroups. After correcting for age, sex, education, EDSS and depression, MSNQ significantly predicted SDMT in the total group, but not the subgroups. MSNQ significantly predicted a positive depression and/or cognitive impairment screen in the total group and all subgroups. The relationship between subjective and objective cognitive screening tools is not influenced by physical disability. MSNQ scores are substantially influenced by depression, and reflect cognitive function to some degree. Patient-reported cognitive measures can be useful to identify patients requiring further (neuro)psychological assessment.

Abstract Background Inclusion body myositis (IBM) is a rare neuromuscular disease (NMD) and effective therapies are not available. Thus, it is relevant to determine the health-related quality of life (HRQoL) in IBM patients including aspects of mental health and illnesses. Objectives To identify and summarize the assessment of HRQoL, mental health and illnesses in IBM, the major factors that determine and influence them as well as the respective influence of IBM in general and compared to other NMD as a systematic review. Methods We performed a mixed methods systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was conducted within the databases PubMed, PsycINFO, LIVIVO and the Cochrane Database. Data were narratively summarized and categorized in the physical, psychological and social HRQoL dimensions. Results The systematic screening totalled 896 articles. Six studies were finally identified, comprising of 586 IBM patients. The applied patient reported outcome measures (PROMs) varied. Quantitatively, the main physical impairments (e.g. weakness, functioning, role perception) were assessed using the general population or other NMD as comparators. Results on social and psychological HRQoL were frequently inconsistent. Qualitatively, psychological and social limitations accompanied IBM related physical deteriorations. Conclusions A research gap exists regarding rigour determinants of HRQoL and mental illness in IBM. In-depth qualitative studies could help to prepare the ground for the assessment of long-term HRQoL data combined with appropriately focussed psychological PROMs advancing the understanding of the HRQoL in IBM throughout the course of the disease from a patient perspective.

Durch die Covid-19-Pandemie hat sich die mentale Gesundheit weltweit verschlechtert. In diesem Zusammenhang ist ein Anstieg an Suizidraten nicht auszuschließen. Suizid-Präventions-Apps könnten den Patienten im Umgang mit Suizidalität helfen. Deshalb wurden Effekte von Suizid-Präventions-Apps auf das Auftreten und die Intensität von Suizidgedanken im Zuge einer Übersichtsarbeit erfasst. Dabei wurden quantitative Studien zu Smartphone-Apps mit dem Endpunkt Suizidgedanken eingeschlossen, die eine Sicherheitsplanfunktion aufwiesen. Vier relevante Studien wurden identifiziert, bei denen das Vorliegen von Bias-Varianten unterschiedlicher Ausprägung angenommen werden muss. Die Ergebnisse zeigten zwar positive Effekte, die aber überwiegend statistisch nicht signifikant waren. Die Ergebnisse dieser Arbeit reihen sich in den bisherigen Stand der Forschung ein. Die geringe Zahl an Studien sowie methodische Schwachstellen limitieren die Aussagekraft der Ergebnisse. Deutschland ist in der Forschung und Entwicklung zu Suizid-Präventions-Apps kaum vertreten. Wenn zukünftig entsprechende internationale Apps als digitale Gesundheitsanwendungen (DiGAs) für das deutsche Gesundheitswesen verfügbar werden, ist davon auszugehen, dass eine Suizidprävention per App positive Effekte bei Suizidalität zeigen werden. Gleichzeitig sollten hochwertige Studien im nationalen Setting die positiven Versorgungseffekte zeitnah bestätigen.