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Background: Effective treatment for neuralgic amyotrophy (NA), a disabling brachial plexus syndrome of supposed immunomediated origin, is currently lacking. Given the circumstantial evidence of a beneficial effect of prednisolone on pain and paresis, this report evaluates the effects of prednisolone treatment administered in the acute phase in a retrospective case series of 50 NA patients. Methods: Baseline variables (eg, age, sex, type of NA and number of attacks), treatment variables (eg, time until treatment, regimen and use of analgesics) and outcome measures (eg, duration and severity of pain, time course and severity of paresis and functional outcome) were statistically analysed and compared with a historical control group of 203 untreated NA patients. Results: The baseline characteristics of the two patient groups were comparable. The median time until initial pain relief was lower in the study group (12.5 days vs 20.5 days), and a significantly higher percentage already recovered strength in the first month of treatment (18% vs 6.3%; p = 0.011). Twelve per cent had fully recovered within 1 year, while this was 1% for the controls (p<0.001), with the proportion reporting a "good" 12-month outcome also being higher (44% vs 10.7%; p<0.001). Side effects were reported by 20%, but none led to a discontinuation of treatment. Conclusion: Oral prednisolone seems effective in the acute phase of neuralgic amyotrophy with the current results supporting previous case reports. A regimen of oral prednisolone is therefore recommended in the acute phase of the syndrome pending a prospective, randomised trial verifying the results obtained. [ABSTRACT FROM AUTHOR]

Purpose: The graphical processing unit (GPU) on modern graphics cards offers the possibility of accelerating arithmetically intensive tasks. By splitting the work into a large number of independent jobs, order-of-magnitude speedups are reported. In this article, the possible speedup of PLATO’s ray tracing algorithm for dose calculations using a GPU is investigated. Methods: A GPU version of the ray tracing algorithm was implemented using NVIDIA’s CUDA, which extends the standard C language with functionality to program graphics cards. The developed algorithm was compared based on the accuracy and speed to a multithreaded version of the PLATO ray tracing algorithm. This comparison was performed for three test geometries, a phantom and two radiotherapy planning CT datasets (a pelvic and a head-and-neck case). For each geometry, four different source positions were evaluated. In addition to this, for the head-and-neck case also a vertex field was evaluated. Results: The GPU algorithm was proven to be more accurate than the PLATO algorithm by elimination of the look-up table for z indices that introduces discretization errors in the reference algorithm. Speedups for ray tracing were found to be in the range of 2.1–10.1, relative to the multithreaded PLATO algorithm running four threads. For dose calculations the speedup measured was in the range of 1.5–6.2. For the speedup of both the ray tracing and the dose calculation, a strong dependency on the tested geometry was found. This dependency is related to the fraction of air within the patient’s bounding box resulting in idle threads. Conclusions: With the use of a GPU, ray tracing for dose calculations can be performed accurately in considerably less time. Ray tracing was accelerated, on average, with a factor of 6 for the evaluated cases. Dose calculation for a single beam can typically be carried out in 0.6–0.9 s for clinically realistic datasets. These findings can be used in conventional planning to enable (nearly) real-time dose calculations. Also the importance for treatment optimization techniques is evident. [ABSTRACT FROM AUTHOR]

Background: little is known about the prevalence rates and correlates of fear of falling and avoidance of activity due to fear of falling in the general population of community-living older people. Objective: to assess prevalence rates and study correlates of fear of falling and avoidance of activity due to fear of falling in this population. Study design and setting: cross-sectional study in 4,031 community-living people aged ≥70 years. Results: fear of falling was reported by 54.3% and associated avoidance of activity by 37.9% of our population. Variables independently associated with fear of falling were: higher age (≥80 years: odds ratio (OR) = 1.79; 95% confidence interval (CI) = 1.49-2.16), female gender (OR = 3.23; 95% CI = 2.76-3.79), poor perceived general health (OR = 6.93; 95% CI = 4.70-10.21) and multiple falls (OR = 5.72; 95% CI = 4.40-7.43). Higher age (≥80 years: OR = 1.92; 95% CI = 1.59-2.32), poor perceived general health (OR = 11.91; 95% CI = 8.38-16.95) and multiple falls (OR = 4.64; 95% CI = 3.73-5.76) were also independently associated with avoidance of activity. Conclusions: fear of falling and avoidance of activities due to fear of falling, were highly prevalent in our sample of community-living older people. Particularly, poor perceived general health showed a strong, independent association with both, fear of falling, and related avoidance of activity. Findings of our study may help health care professionals to identify people eligible for interventions aimed at reducing fear of falling and activity restriction. [ABSTRACT FROM AUTHOR]

Abstract: So far, guide ways for positioning systems (stages) in semiconductor applications are often equipped with air bearings and/or roller bearings. Although these passive bearing systems are seemingly rather cost-effective, motion performance and motion capabilities are limited compared to active systems using multiple servo loops. So far, nm-level motion performance in 6 degrees of freedom (DoF) was realized through the application of an isolated machine architecture in combination with a hybrid stage concept, i.e., by stacking an active short stroke system providing fine adjustments on top of a passive long stroke system. This paper describes the development of a full 6-DoF active positioning system with nm-level motion performance in one single (long stroke) stage, using active magnetic bearing systems. It is shown that active bearings provide interesting advantages and additional features for substrate positioning, enabling a rather simple and cost effective stage design, suitable for next generation semiconductor applications. [Copyright &y& Elsevier]

Aims--To assess the occurrence of infantile colic in the community and the need for professional help; and to study the influences of potential determinants of infantile colic. Methods--Surveys were identified by a systematic search in Medline (1966-98) and Embase (1988-98). Retrieved publications were checked for references. Studies selected were community based, prospective, and retrospective surveys on the occurrence of infantile colic published in English, German, French, or Dutch. Occurrence rates were calculated as percent- ages. Methodological quality of the surveys was assessed by two assessors independently with a standardised criteria list containing items on method of data gathering, definition of colic, and drop out rate. Results--Fifteen community based surveys were identified. The methodological quality varied considerably and was generally low. Even the two most methodologically sound prospective studies yielded widely varying cumulative incidence rates of 5-19%. Referral rates or the need to seek help because of crying were consistently lower than occurrence rates for prolonged crying as such. Gender, socio-economic class, type of feeding, family history of atopy, and parental smoking were not shown to be associated with colic. Conclusion--Occurrence rates of infantile colic vary greatly according to methodological quality. A considerable number of parents reporting prolonged crying do not seek or need professional help. [ABSTRACT FROM AUTHOR]

This study compares the reproducibility, construct validity and responsiveness of self-report and parent-report quality of life questionnaires How Are You (HAY) for 8-12-year-old children with asthma. A total of 228 Dutch children with asthma and their parents completed the HAY and daily recorded the child's asthma symptoms in a diary. Additionally 296 age- and -gender matched healthy children and their parents completed the generic part of the HAY. Reproducibility and responsiveness were examined in a sub-group of 80 children with asthma. In this group, three measurements were carried out, at baseline, after one week and once during the following 6 month when the clinical asthma status had changed. The within-subject standard deviations (SD) of three dimensions (physical activities, social activities, self-management) differed significantly (p < 0.05) in favour of the parent-version, indicating that the reproducibility of the parent version was better than that of the child version. The mean score-differences between children with asthma and healthy children as reported by parents did not significantly differ from those reported by children, except for cognitive activities (e.g. be able to concentrate on school work). The mean differences with regard to children with a different actual asthma status (symptom analysis), as reported by both informants, did not differ. Compared to the child-version, the parent-version showed greater ability to detect changes in children's quality of life over time for all but one dimension, indicating better responsiveness. The results indicate that in discriminative studies child and parents reports can be substituted on a group-level. In longitudinal studies data have to be obtained from parents. Consequently, caregivers collecting quality of life data for longitudinal purposes in daily practice should collect these data simply from parents. [ABSTRACT FROM AUTHOR]

Structural and calorimetric investigation of GexTe100-x films over wide range of concentration 10 < x < 50 led to evidence two structural singularities at x ~ 22 at. % and x ~ 33-35 at. %. Analysis of bond distribution, bond variability, and glass thermal stability led to conclude to the origin of the first singularity being the flexible/rigid transition proposed in the framework of rigidity model and the origin of the second one being the disappearance of the undercooled region resulting in amorphous materials with statistical distributions of bonds. While the first singularity signs the onset of the Ge-Ge homopolar bonds, the second is related to compositions where enhanced Ge-Ge correlations at intermediate lengthscales (7.7 Å) are observed. These two threshold compositions correspond to recently reported resistance drift threshold compositions, an important support for models pointing the breaking of homopolar Ge-Ge bonds as the main phenomenon behind the ageing of phase change materials. [ABSTRACT FROM AUTHOR]

Objective: To determine whether second-trimester cervical length (CL) in women with a twin pregnancy is associated with the risk of emergency Cesarean section.Methods: This was a secondary analysis of two randomized trials conducted in 57 hospitals in The Netherlands. We assessed the univariable association between risk indicators, including second-trimester CL in quartiles, and emergency Cesarean delivery using a logistic regression model. For multivariable analysis, we assessed whether adjustment for other risk indicators altered the associations found in univariable (unadjusted) analysis. Separate analyses were performed for suspected fetal distress and failure to progress in labor as indications for Cesarean section.Results: In total, 311 women with a twin pregnancy attempted vaginal delivery after 34 weeks' gestation. Emergency Cesarean delivery was performed in 111 (36%) women, of which 67 (60%) were performed owing to arrest of labor. There was no relationship between second-trimester CL and Cesarean delivery (adjusted odds ratio (aOR): 0.97 for CL 26(th) -50(th) percentiles; 0.71 for CL 51(st)  - 75(th) percentiles; and 0.92 for CL > 75(th) percentile, using CL ≤ 25(th) percentile as reference). In multivariable analysis, the only variables associated with emergency Cesarean delivery were maternal age (aOR, 1.07 (95% CI, 1.00-1.13)), body mass index (BMI) (aOR, 3.99 (95% CI, 1.07-14.9) for BMI 20-23 kg/m(2) ; 5.04 (95% CI, 1.34-19.03) for BMI 24-28 kg/m(2) ; and 3.1 (95% CI, 0.65-14.78) for BMI > 28 kg/m(2) ) and induction of labor (aOR, 1.92 (95% CI, 1.05-3.5)).Conclusion: In nulliparous women with a twin pregnancy, second-trimester CL is not associated with risk of emergency Cesarean delivery. [ABSTRACT FROM AUTHOR]

Abstract: We fabricated arrays of cantilever sensors suspended deep inside fluid wells. To eliminate critical alignment and assembling steps during encapsulation of the cantilevers, these 3-D MEMS devices are realized in a single-side, single-wafer process by employing photolithography on bulk micromachined substrates. Silicon nitride cantilevers with varying geometries are suspended up to below the wafer surface, and a structured gold layer is patterned on top. After calibrating the cantilevers in an optical lever setup, the formation of a DNA monolayer on the cantilever surface is detected. [Copyright &y& Elsevier]

Abstract: In piezoelectric positioning systems the achievable bandwidth is often limited by weakly damped resonant modes. System performance may be improved by avoiding the excitation of these modes. If sufficient mechanical damping is present this can be done by shifting resonant modes towards anti-resonant modes through manipulation of the mechanical boundary conditions. In a second approach the anti-resonances may be shifted towards the resonances by the application of modal actuation. Using this method the excitation of the second and higher order modes can be avoided by adjusting the distribution of actuation forces. This paper investigates and compares the application of modal control techniques in systems that are based on piezoelectric tube actuators such as atomic force microscopes. [Copyright &y& Elsevier]

Abstract: In this paper a new contactless transport system for thin, flat products, such as silicon wafers, is introduced. The product is carried on a thin aerostatic film between the product and the transport system and transported along the system using viscous traction on the product surface. This viscous traction is the result of pressure driven air flow in an array of actuator cells. Several possible industrial applications are discussed, followed by an explanation of the operating principles. Furthermore an analytical model of the system is presented, together with computational results. Numerical modeling using FEA, solving for the incompressible Navier–Stokes equations, shows results that are in good agreement with the described analytical model and some experimental results. The maximum acceleration and vertical bearing stiffness that can be obtained for the considered actuator geometry meet the requirements for the considered industrial applications. [Copyright &y& Elsevier]

Background: There is much evidence for the influence of low socio-economic status on poor health. It is, however, also important to study the ways in which people attain and retain their socio-economic status and the factors that predict changes in socio-economic status, such as a decrease in income. Such mobility also occurs in older populations, in which financial and health-related changes are very common, especially after retirement. Methods: Three years of follow-up data from 1443 Dutch men and women aged 55 years and older who participated in the Study on Medical Information and Lifestyles Eindhoven (SMILE) were gathered. Logistic regression analyses were used to study the independent effects of physical and mental dysfunction and severity of chronic diseases and adverse personality factors on decrease in income. Results: Social anxiety (OR = 1.62, 95% CI: 1.09-2.40), physical dysfunction (OR=1.71, 95% CI: 1.07-2.74) and severe diseases (OR=1.37, 95% CI: 1.05-1.78) were significant predictors of decrease in income. These contributions were independent of each other, and remained robust after controlling for other confounding factors, such as gender, age and educational level and change in employment status. Mental dysfunction and other personality characteristics, such as hostility and mastery, did not contribute to decrease in income. Conclusion: Social anxiety and poor physical health are relevant factors associated with decrease in income in old age. The findings suggest that these factors are important in retaining one's socio-economic status. Future longitudinal research is necessary to further disentangle the mechanisms and pathways related to socio-economic health inequalities along the life-course. [ABSTRACT FROM AUTHOR]

Abstract: A method is described to integrate particle filters inside a silicon wafer by creating pores in a recessed membrane. The filters are created in either a silicon or a silicon nitride membrane located 100μm below the wafer surface. The fabrication process involves anisotropic etching of front- and back-side of a (100) silicon wafer, deposition of a silicon nitride layer, spraycoating of photoresist and reactive ion etching of the pores. The filters may serve as a well or reaction chamber at the same time. We have patterned pore diameters in the 10–50μm range in 100μm recessed membranes that are suitable for application in stacked systems such as in an integrated inkjet nozzle. [Copyright &y& Elsevier]

Objective: Sufficient psychosocial coping resources and an adequate coping style may have a beneficial influence on quality of life in patients with a chronic disease. Until now little research has been directed at these associations and particularly not among patients with asthma or chronic obstructive pulmonary disease (COPD). The objective of this study is to examine the association between psychosocial coping resources and coping style with HRQoL, for asthma and COPD separately.Methods: Fourteen general practitioners in The Netherlands recruited 273 adult patients with asthma (n = 220) or COPD (n = 53). Data were collected by a pulmonary function assessment, a face-to-face interview and validated questionnaires about psychosocial coping resources (self-efficacy, mastery, self-esteem, and social support), coping style (avoidant, rational and emotional), and health related quality of life (HRQoL).Results: A more emotional coping style (p < 0.01) was independently associated with poor HRQoL in both asthma and COPD patients. Furthermore, in asthma patients, less self-efficacy feelings (p < 0.01), less mastery feelings (p = 0.05), a more avoidant coping style (p = 0.04) and poor pulmonary function (p < 0.01) were independently associated with poor HRQoL. In COPD patients, a more rational coping style (p = 0.02) was independently associated with poor HRQoL.Conclusion: Our findings suggest that psychosocial coping resources and coping style are independently associated with HRQoL in patients with asthma or COPD. Further research should explore the possibilities of intervening on these factors, aiming to improve HRQoL in patients with asthma or COPD. [ABSTRACT FROM AUTHOR]

Abstract Aims To longitudinally assess risk factors for diabetic polyneuropathy (DPN) severity, and to longitudinally assess risk factors for the change of DPN severity during 2–4 years of follow-up. Methods From 1995 to 1999, 486 Type 2 diabetes patients in general practice were examined annually with regard to DPN severity and its possible risk factors. DPN severity was assessed with a clinical neurological examination (CNE) which included pinprick sense, light touch sense, vibration sense and ankle jerk. Longitudinal (multivariate) linear associations of (change of) CNE score and predicting variables were analysed using multilevel analyses. Results In this population, 50% of participants were men and had a mean age of 65.4 years, almost one-third (31.7%) of the participants had a CNE score > 4 at baseline and were classified with DPN. CNE score significantly increased during follow-up. Among participants not graded with DPN at baseline, 21.3% progressed towards a CNE score > 4 after 3 years of follow-up. Longitudinal multivariate analyses showed that age, diabetes duration, HbA1c , height, body mass index and ankle-arm index together best predicted CNE score during follow-up. Change of CNE score during follow-up was best predicted by age, diabetes duration and HbA 1c , with the latter being the strongest predictor. Conclusions Although several factors are longitudinally associated with DPN, HbA1c , age and diabetes duration were the best predictors of CNE change during follow-up. Therefore, improving glycaemia remains an important amenable factor in preventing worsening of diabetic polyneuropathy. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to examine whether work capabilities differ between workers with Multiple Sclerosis (MS) and workers from the general population. The second aim was to investigate whether the capability set was related to work and health outcomes.Methods: A total of 163 workers with MS from the MS@Work study and 163 workers from the general population were matched for gender, age, educational level and working hours. All participants completed online questionnaires on demographics, health and work functioning. The Capability Set for Work Questionnaire was used to explore whether a set of seven work values is considered valuable (A), is enabled in the work context (B), and can be achieved by the individual (C). When all three criteria are met a work value can be considered part of the individual's 'capability set'.Results: Group differences and relationships with work and health outcomes were examined. Despite lower physical work functioning (U = 4250, p = 0.001), lower work ability (U = 10591, p = 0.006) and worse self-reported health (U = 9091, p ≤ 0.001) workers with MS had a larger capability set (U = 9649, p ≤ 0.001) than the general population. In workers with MS, a larger capability set was associated with better flexible work functioning (r = 0.30), work ability (r = 0.25), self-rated health (r = 0.25); and with less absenteeism (r = - 0.26), presenteeism (r = - 0.31), cognitive/neuropsychiatric impairment (r = - 0.35), depression (r = - 0.43), anxiety (r = - 0.31) and fatigue (r = - 0.34).Conclusions: Workers with MS have a larger capability set than workers from the general population. In workers with MS a larger capability set was associated with better work and health outcomes.Trial Registration: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. The study is registered at the Dutch CCMO register ( https://www.toetsingonline.nl ). This study is approved by the METC Brabant, 12 February 2014. First participants are enrolled 1st of March 2014. [ABSTRACT FROM AUTHOR]

Telemedicine in heart failure (HF) management may positively impact health outcomes, but varied effects in studies hinder guidance in HF guidelines. Evidence on the effectiveness of telemedicine in HF subpopulations is limited. We conducted a scoping review to evaluate and synthesise evidence on the effectiveness of telemedicine across HF subpopulations that could guide telemedicine strategies in routine practice. Meta-analyses concerning randomised controlled trials (RCTs) with subgroup analyses on telemedicine effectives were identified in PubMed. We identified 15 RCTs, encompassing 21 different subgroups based on characteristics of HF patients. Findings varied across studies and no definite evidence was found about which patients benefit most from telemedicine. Subgroup definitions were inconsistent, not always a priori defined and subgroups contained few patients. Some studies found heterogeneous effects of telemedicine on mortality and hospitalisation across subgroups defined by: New York Heart Association (NYHA) classification, previous HF decompensation, implantable device, concurrent depression, time since hospital discharge and duration of HF. Patients represented in the RCTs were mostly male, aged 65-75 years, with HF with reduced ejection fraction and NYHA class II/III. Traditional RCTs have not been able to provide clinicians with guidance; continuous real-world evidence generation could enhance monitoring and identify who benefits from telemedicine., (© 2024. The Author(s).)

Objective: To describe the experiences of healthcare professionals with integrating telemedicine in routine heart failure (HF) care., Methods: Semi-structured interviews were conducted with healthcare professionals ( n  = 19) in the Netherlands who were involved in decision-making, implementation or routine use of telemedicine in HF management. Using purposive sampling, nurses, cardiologists and managers were selected to be interviewed. Interviews were performed in-person, recorded and transcribed verbatim. Interview data were analysed using a reflexive thematic analysis., Results: This study identified four themes: (1) Responsibility - the lack of a clear delineation of roles and responsibilities among healthcare professionals, patients and suppliers in telemedicine. (2) Confidence and safety - telemedicine is seen by healthcare professionals as capable of enhancing safety, yet also introduces the risk of fostering a false sense of security among patients. (3) Collaboration - actively involving end-users in the development and implementation of telemedicine promotes the adoption. (4) Processes and mutual agreements - rather than replacing traditional care, telemedicine is perceived as an adjunct to it. Structured care pathways support telemedicine implementation, and personalised telemedicine can empower patients in self-care., Conclusions: Telemedicine is a promising intervention in the management of HF. However, existing systems and care pathways have resulted in limited adoption. Improvements in the collaboration and establishing clear agreements on responsibilities between professional, patient and supplier can lead to more confidence in adopting telemedicine. Structured care pathways can be supportive. A personalised telemedicine approach can ensure that telemedicine remains manageable for patient and professional., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Cardiac fibrosis is increasingly recognized as a marker of worse outcomes in long-term follow-up after heart transplantation (HTX). We investigated the clinical determinants and biomarkers of focal and interstitial cardiac fibrosis as assessed with cardiac magnetic resonance (CMR)., Methods: Consecutive HTX recipients underwent CMR with late gadolinium enhancement for focal myocardial fibrosis and T1 mapping for interstitial fibrosis. We calculated the correlations of these findings with clinical parameters, history, biomarkers of fibrosis (B-type natriuretic peptide (BNP), growth differentiation factor-15, galectin-3 and soluble ligand ST2) and echocardiography., Results: Forty-eight HTX patients were included: median age 63 ± 13 years, 11 ± 6 years after heart transplantation. Only donor weight (p 0.044) and the rate of a > 30 % mismatch between donor and recipient weight (p 0.02) were significantly different in patients with vs. without late LGE. Extracellular volume (ECV) was correlated with the weight mismatch between donor and recipient (r = 0.32, p 0.04), resulting in a higher ECV for oversized donors. BNP was the only biomarker of the four studied that was correlated with interstitial fibrosis as assessed by ECV (r = 0.35, p 0.04). T1 relaxation time was correlated with treated acute cellular rejection grade ≥ 2 (ISHLT grading) (r = 0.34, p 0.02)., Conclusion: Both focal and interstitial fibrosis, as determined by CMR, after heart transplantation are correlated with donor and recipient weight mismatch. BNP was the only biomarker clinically relevant to interstitial cardiac fibrosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background and Objectives: Wearing-off symptoms during natalizumab treatment in multiple sclerosis are characterized by an increase of MS-related symptoms prior to natalizumab administration. The influence of extended interval dosing (EID) on wearing-off symptoms are important to consider, as this might cause hesitancy in initiating or continuing EID., Methods: Participants of the NEXT-MS trial, in which treatment intervals are adjusted based on drug concentrations, were divided into two groups: an extended group containing participants with at least one week of additional interval extension, and a group with a fixed interval during the trial (range 4-7 weeks). Changes in the occurrence, frequency, onset, and severity of wearing-off symptoms were evaluated., Results: 255 participants were included (extended group n = 171, fixed group n = 84). The odds on occurrence of wearing-off symptoms in the extended group did not increase after extending the treatment interval. Additional analyses for frequency, onset, and severity of wearing-off symptoms showed no changes over time. Mean decrease in natalizumab drug concentration did not influence the frequency of wearing-off symptoms., Discussion: Wearing-off symptoms were not reinforced by further extending the natalizumab interval. Wearing-off symptoms might increase in a minority of patients after EID, although our data support the view that wearing-off symptoms appear to be unrelated to the decrease in natalizumab trough drug concentrations., Competing Interests: Declaration of competing interest A.A. Toorop: nothing to disclose. M.H.J. Wessels: nothing to disclose. L.M.Y. Gelissen: nothing to disclose. E. Hoitsma: has accepted (speaker and congress) fees from Merck Serono, Biogen Idec, Roche, and Sanofi Genzyme. E.M.P.E. Zeinstra: reports advisory boards/consultancy fees for Merck, Novartis, Genzyme and Roche. L.C. van Rooij: nothing to disclose. C.E.P. van Munster: nothing to disclose. A. Vennegoor: nothing to disclose. J.P. Mostert: nothing to disclose. B.H.A. Wokke: nothing to disclose. N.F. Kalkers: nothing to disclose. E.L.J. Hoogervorst: nothing to disclose. J.J.J. van Eijk: reports honoraria for advisory boards and/or speakers fee from Merck Serono, Biogen Idec, Sanofi Genzyme, Roche and Novartis. C.M. Roosendaal: nothing to disclose. J.J. Kragt: nothing to disclose. M. Eurelings: nothing to disclose. J. Nielsen: nothing to disclose. J. van Genugten: nothing to disclose. L.G.F. Sinnige: nothing to disclose. M.E. Kloosterziel: nothing to disclose. E.P.J. Arnoldus: nothing to disclose. G.W. van Dijk: nothing to disclose. W.H. Bouvy: nothing to disclose. E.M.M. Strijbis: nothing to disclose. B.W. van Oosten: nothing to disclose. B.A. de Jong: nothing to disclose. B.I. Lissenberg-Witte: nothing to disclose. T. Rispens received funding for research from Genmab and consultancy fees from Novartis. B.M.J. Uitdehaag: reports research support and/or consultancy fees from Genzyme, Biogen Idec, Novartis, Teva Pharmaceutical Industries, Merck Serono, Roche, and Immunic Therapeutics. J. Killestein: received research grants for multicentre investigator initiated trials DOT-MS trial, ClinicalTrials.gov Identifier: NCT04260711 (ZonMW) and BLOOMS trial (ZonMW and Treatmeds), ClinicalTrials.gov Identifier: NCT05296161); received consulting fees for F. Hoffmann-La Roche Ltd., Biogen, Teva, Merck, Novartis and Sanofi/Genzyme (all payments to institution); reports speaker relationships with F. Hoffmann-La Roche Ltd., Biogen, Immunic, Teva, Merck, Novartis and Sanofi/Genzyme (all payments to institution); adjudication committee of MS clinical trial of Immunic (payments to institution only). Z.L.E. van Kempen: nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To investigate longitudinal relationships between employment status and disease-related, (neuro)psychological, and work-related factors in people with multiple sclerosis (MS)., Methods: 170 employed people with MS underwent yearly neurological and neuropsychological examinations to assess MS-related disability and cognitive functioning. Additionally, they completed yearly questionnaires assessing depression, anxiety, fatigue, cognitive complaints, workplace support and coping. Multilevel models for change were fitted to examine progression of these factors over three years, and to assess possible relationships with change in employment status., Results: People with a deteriorated employment status after three years reported more depression ( p= 0.009), a higher impact of fatigue ( p< 0.001), more cognitive complaints ( p< 0.001) and less workplace support ( p= 0.001) at baseline than people with a stable employment status. There were no differences in progression over time of the examined variables between people with a stable or deteriorated employment status., Conclusion: More depression, a higher impact of fatigue, more cognitive complaints and less workplace support are predictive of a deteriorated employment status after three years in individuals with MS. How these factors progress over time is not different between those with a stable or deteriorated employment. MS-related disability, anxiety, objective cognition and coping were not related to a deterioration in employment status., Competing Interests: E.E.A. van Egmond, K. van der Hiele, M.J. de Rooij, D.A.M. van Gorp, J.J.L. van der Klink, M.F. Reneman, E.A.C. Beenakker, S.T.F.M. Frequin, K. de Gans, O.H.H. Gerlach, J.P. Mostert, and H.A.M. Middelkoop declare no conflict of interestP.J. Jongen received honoraria from Bayer Netherlands and Orikami Personalized Health Care for consultancy activities and is chairman of the MSmonitor Foundation.L.H. Visser received a research grant for the multicentre BIA study from Merck, received consultancy fees from Merck, Novartis and JanssenJ.J.J. van Eijk received consultancy fees and honoraria for lectures from Merck, Biogen, Novartis, Sanofi, Janssen and RocheE. Hoitsma received honoraria for lectures and advisory boards from Bayer, Biogen, Roche, Sanofi Genzyme, Merck Serono, Novartis and Teva.W.I.M. Verhagen received consultancy fees from Merck and Biogen, (© 2024 The Authors.)

Introduction: Meta-analyses show postive effects of telemedicine in heart failure (HF) management on hospitalisation, mortality and costs. However, these effects are heterogeneous due to variation in the included HF population, the telemedicine components and the quality of the comparator usual care. Still, telemedicine is gaining acceptance in HF management. The current nationwide study aims to identify (1) in which subgroup(s) of patients with HF telemedicine is (cost-)effective and (2) which components of telemedicine are most (cost-)effective., Methods and Analysis: The RELEASE-HF ('REsponsible roLl-out of E-heAlth through Systematic Evaluation - Heart Failure') study is a multicentre, observational, registry-based cohort study that plans to enrol 6480 patients with HF using data from the HF registry facilitated by the Netherlands Heart Registration. Collected data include patient characteristics, treatment information and clinical outcomes, and are measured at HF diagnosis and at 6 and 12 months afterwards. The components of telemedicine are described at the hospital level based on closed-ended interviews with clinicians and at the patient level based on additional data extracted from electronic health records and telemedicine-generated data. The costs of telemedicine are calculated using registration data and interviews with clinicians and finance department staff. To overcome missing data, additional national databases will be linked to the HF registry if feasible. Heterogeneity of the effects of offering telemedicine compared with not offering on days alive without unplanned hospitalisations in 1 year is assessed across predefined patient characteristics using exploratory stratified analyses. The effects of telemedicine components are assessed by fitting separate models for component contrasts., Ethics and Dissemination: The study has been approved by the Medical Ethics Committee 2021 of the University Medical Center Utrecht (the Netherlands). Results will be published in peer-reviewed journals and presented at (inter)national conferences. Effective telemedicine scenarios will be proposed among hospitals throughout the country and abroad, if applicable and feasible., Trial Registration Number: NCT05654961., Competing Interests: Competing interests: JB received an independent research grant from Abbott for ISS paid to institution, and has had speaker engagements or advisory boards for AstraZeneca, Abbott, Bayer, Boehringer, Daiichi Sankyo, Novartis and Vifor in the past 5 years. RAdB has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals, Ionis Pharmaceuticals, Novo Nordisk and Roche, and has had speaker engagements with Abbott, AstraZeneca, Bayer, Bristol Myers Squibb, Novartis and Roche. CJWB has received speaker fees from AstraZeneca, Boehringer Ingelheim and Novartis. MLH is supported by the Dutch Heart Foundation (Dr E Dekker Senior Clinical Scientist Grant 2020T058) and CVON (2020B008 RECONNEXT). He received an investigator-initiated research grant from Vifor Pharma, an educational grant from Boehringer Ingelheim and Novartis, and speaker/consultancy fees from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, MSD, Novartis, Sankyo, Daiichi, Quinn and Vifor Pharma, all of which were not related to this study., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To assess the internal and external validity of a cluster randomized controlled trial (cRCT) evaluating a decision tool with supportive interventions for the empirical treatment of urinary tract infections (UTIs) in nursing homes (NHs), and to identify facilitators and barriers in implementing this antibiotic stewardship intervention., Design: Mixed-methods process evaluation study., Setting and Participants: Physicians, nursing staff, client council members, and residents of Dutch NHs., Methods: We used cRCT data of the ANNA study (Antibiotic Prescribing and Non-prescribing in Nursing Home Residents With Signs and Symptoms Ascribed to Urinary Tract Infection). In addition, we sent out an online evaluation questionnaire, conducted semistructured interviews with physicians and nursing staff, and consulted client council members., Results: Internal validity was lowered: control group physicians participated in several non-study-related activities regarding UTI. External validity was good: almost all intervention components had a high fidelity (52%-74%) and were perceived as relevant (physicians: 7.2-8.6 of 10, nursing staff: 6.5-8.5 of 10) and feasible (physicians: 7.5 of 10, nursing staff 6.4 of 10), with feasibility for residents with dementia and urine incontinence needing attention. The most common reason for deviating from the advice generated by the decision tool was an unclear illness presentation. Identified facilitators to implementation were confidence in the intervention, repeated intervention encounter, and having "champions" in the NH. Barriers were limited involvement of nursing staff, unstable nursing teams, residents' and representatives' belief that antibiotics should be prescribed, and a low antibiotic prescribing threshold within the NH culture., Conclusions and Implications: Lowered internal validity may have reduced the study effect. Attention should be paid to the feasibility of the intervention in residents with dementia and urinary incontinence. Improvement opportunities for implementation were higher nursing staff involvement and repeated intervention offering., Competing Interests: Disclosure SG reports participation in an advisory board concerning intravenous administration of temocillin in 2019. The other authors have no competing interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Antibiotics are often inappropriately prescribed for urinary tract infections (UTIs) in nursing home (NH) residents. Research emphasises the importance of prescribing antibiotics only if there are UTI-related signs and symptoms (S&S). However, for many NH residents it is challenging to find out whether such S&S are present, for example due to cognitive disorders., Objectives: To provide insight into the assessment of UTI-related S&S in NH residents with impaired awareness or ability to communicate S&S, and to develop supportive tools for the observation of UTI-related S&S in this subgroup of NH residents, by nursing staff., Methods: We performed a practice-based study using mixed methods. Data of 295 cases of suspected UTI were analysed to determine how often UTI-related S&S were 'not assessed/non-assessable' in residents with and without dementia. Barriers and facilitators in observing UTI-related S&S in NH residents with impaired awareness or ability to communicate S&S were derived from interviews and focus groups with nursing staff. Literature review, focus group data, additional telephone interviews and questionnaires with nursing staff were used in a step-by-step process, including pilot testing, to develop supportive tools for the observation of UTI-related S&S., Results: UTI-related S&S were assessable in the majority of NH residents with dementia. The proportion 'not assessed/non-assessable' S&S in residents with dementia increased with increasing severity of dementia. In residents with very severe dementia, up to 58% of the S&S were 'not assessed/non-assessable'. Knowing the resident, working methodologically, and being sufficiently skilled to interpret observations in residents facilitate the assessment of UTI-related S&S. Insights acquired during the different study elements resulted in the development of an observation checklist and a 24-h observation tool., Conclusions: The more NH residents have impaired awareness of ability to communicate S&S, the more difficult it seems to be to assess UTI-related S&S. The observation checklist and 24-h observation tool developed in the current study may support nursing staff in their observation of UTI-related S&S in this group of NH residents., (© 2023 The Authors. International Journal of Older People Nursing published by John Wiley & Sons Ltd.)

Previous research discovered a protective effect of higher conscientiousness against a 3-year deterioration in employment status in persons with multiple sclerosis (pwMS). To replicate these findings, we used data from a multicentre prospective cohort study where 145 employed pwMS completed questionnaires, neurological and neuropsychological examinations at baseline and after 3 years. A 3-year deterioration in employment status was reported in 31.0%. We observed no differences in personality, demographics or clinical characteristics between pwMS with deteriorated or stable employment status. These null findings may be partly explained by the classification of deteriorated employment status, which does not reflect Dutch labour conditions., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: PJJ received honoraria from Bayer Netherlands and Orikami Personalized Health Care, the Netherlands, for consultancy activities and is chairman of the MSmonitor foundation, the Netherlands. JJJvE received honoraria for lectures and honoraria for advisory boards from Sanofi Genzyme, Roche, Merck Serono, Novartis. STFMF received honoraria for lectures, grants for research and honoraria for advisory boards from Sanofi Genzyme, Merck Serono, Novartis, Biogen. EH received honoraria for lectures and advisory boards, and grants for research from Bayer, Biogen, Roche, Sanofi Genzyme, Merck Serono, Novartis. WIMV received honoraria for lectures from Biogen and Merck Serono, reimbursement for hospitality from Biogen, Sanofi Genzyme and Merck Serono, and honoraria for advisory boards from Merck Serono. LHV received honoraria for lectures and honoraria for advisory boards from Merck Serono and Novartis., (© The Author(s), 2022.)

Background To improve nutritional care for community-dwelling older adults before, during, and after hospitalization, factors influencing nurses' current behavior should be targeted. The aim of this study was to obtain expert consensus on which factors influencing the behavior of hospital and home care nurses are most relevant, modifiable, and feasible to influence. Method In a two-round Delphi study, nine pre-selected factors were rated by 26 experts. Results Eight factors were rated as relevant, modifiable, and feasible to influence: (1) lack of sufficient knowledge, (2) mainly neutral attitude, (3) low prioritization, (4) ambiguous motivation to routinely use guidelines and screening tools, (5) moderate awareness about risk factors, (6) lack of sense of involving informal caregivers, (7) ambiguous motivation to follow education and training, and (8) strong focus on medical nutrition. Conclusion The expert panel reached consensus on eight factors influencing nurses' current behavior. To enhance nutritional care to prevent malnutrition in older adults, strategies are needed for targeting these factors in nursing practice, education, and research. [ J Contin Educ Nurs . 2022;53(12):545-556.] .

Background: Unemployment is common among people with multiple sclerosis (pwMS) and has been associated with subjective cognitive difficulties, specifically in memory, attention, and executive functioning. However, longitudinal research on subjective cognitive difficulties and employment is scarce., Objective: We investigated whether subjective cognitive impairment (SCI), based on the clinical cut-off score of the MS Neuropsychological Screening Questionnaire (MSNQ), was associated with work status and negative work events (NWE) at baseline and after 2 years. Moreover, we investigated whether four MSNQ subdomains were related to work status and NWE., Methods: 287 participants (77.4% female, median age = 42 years) completed questionnaires on subjective cognitive functioning, depression, anxiety, and fatigue, and completed the Symbol Digit Modalities Test (SDMT). After baseline comparisons, logistic regression analyses were performed, with work status and NWE at baseline, and employment change and NWE change within 2 years after baseline as dependent variables. Independent variables included SCI and the MSNQ domains. Covariates anxiety, depression, fatigue, and SDMT were added., Results: SCI, depression and anxiety were associated with work status ( Nagelkerke R 2 = .286), but only SCI was associated with employment change ( Nagelkerke R 2 = .164). No predictors were associated with NWE at baseline or follow-up. In addition, no MSNQ subdomain was related to work status, employment change or NWE., Conclusion: Unemployed pwMS and pwMS with a deteriorated work status reported more cognitive difficulties after 2 years than employed pwMS or pwMS with a stable work status. In addition, depression, and anxiety were associated with work status., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Background: Symptoms of anxiety and depression affect the daily life of people with multiple sclerosis (MS). This study examined work difficulties and their relationship with anxiety, depression and coping style in people with MS., Methods: 219 employed people with MS (median age  =  43 years, 79% female) completed questionnaires on anxiety, depression, coping style, demographics and work difficulties, and underwent a neurological examination. Two regression analyses were performed with work difficulties as the dependent variable and either anxiety or depression as continuous independent variables. Coping style, age, gender, educational level, MS-related disability and disease duration were added as additional predictors, as well as interaction terms between coping style and either symptoms of depression or anxiety., Results: A significant model was found ( F (10,205)   =  13.14, p  < 0.001, R 2   =  0.39) in which anxiety, emotion- and avoidance-oriented coping and MS-related disability were positively related to work difficulties. The analysis of depression resulted in a significant model ( F (10,205)   =  14.98, p  < 0.001, R 2   =  0.42) in which depression, emotion- and avoidance-oriented coping and MS-related disability were positively related to work difficulties. None of the interaction effects were significant., Conclusions: Work difficulties were positively related to anxiety, depression, emotion- and avoidance-oriented coping and MS-related disability in workers with MS., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Disclosure: E. van Egmond, K. van der Hiele, D. van Gorp, J. van der Klink, M. Reneman, E. Beenakker, K. de Gans, B.M. van Geel, O. Gerlach, J. Mostert, and H. Middelkoop report no conflict of interest. P. Jongen received honoraria from Bayer Netherlands and Orikami Personalized Health Care, Netherlands, for consultancy activities and is chairman of the MSmonitor foundation, Netherlands. J. van Eijk received honoraria for lectures and honoraria for advisory boards from Sanofi Genzyme, Roche, Merck Serono, Novartis and Teva. S. Frequin received honoraria for lectures, grants for research and honoraria for advisory boards from Sanofi Genzyme, Merck Serono, Novartis, Biogen and Roche. G. Hengstman has received consultation fees and grants from Biogen, BMS, Genzyme-Sanofi, Merck BV, Novartis Pharma and Roche. W. Verhagen received honoraria for lectures from Biogen and Merck Serono, reimbursement for hospitality from Biogen, Sanofi Genzyme and Merck Serono, and honoraria for advisory boards from Merck Serono. L.H. Visser received honoraria for lectures and honoraria for advisory boards from Merck Serono and Novartis., (© The Author(s), 2022.)

Background: Multiple sclerosis (MS) poses a major threat to sustainable employability. Identifying conditions and factors that promote work participation is of great importance. Our objective was to explore the contribution of personality traits in explaining occupational functioning in MS., Methods: 241 participants with relapsing-remitting MS (78% female, median age: 42.0 years, median EDSS: 2.0) and 60 healthy controls (70% female, median age: 45.0 years) underwent neuropsychological and neurological examinations and completed questionnaires. Multivariate logistic and linear regression analyses were conducted to examine relations between personality traits and self-reported occupational functioning, while accounting for known correlates., Results: Personality traits were not associated with self-reported occupational functioning when correcting for known correlates. A higher impact of fatigue (B = -0.05, p = .005 and B = -0.04, p = .009) and depression (B = -0.22, p = .008 and B = -0.21, p = .01) were associated with no paid job (R 2  = 0.13) and considering to reduce work hours (R 2  = 0.12). A higher impact of fatigue (B = -0.05, p = .008, β = 0.46, p = .001 and β = -0.36, p = .001) was associated with absenteeism from work (R 2  = 0.15), more presenteeism (R 2  = 0.35) and lower work ability (R 2  = 0.25). A higher impact of fatigue (β = 0.46, p = .001) and anxiety (β = 0.25, p = .001) were associated with more work difficulties (R 2  = 0.54)., Conclusion: Personality traits did not explain additional variance in self-reported occupational functioning in persons with relapsing-remitting MS with mild disability. The impact of fatigue was the main and most consistent correlate of occupational functioning, often combined with depression or anxiety. Total explained variance of the models was limited, emphasizing the need to additionally examine other (contextual) factors when considering occupational challenges in MS., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Specialized rehabilitation following acquired brain injury provides intensive multidisciplinary treatment to individuals with complex disabilities for optimizing recovery and supporting a safe transition to the community. Post-specialist rehabilitation, patients and caregivers have reported a need for support. We present the design of an implementation study to evaluate a new self-management support service for individuals with acquired brain injury and their caregivers. Methods: This is a pre-post intervention study with a mixed-method design. The study population comprises individuals aged ≥18 years with acquired brain injury living independently following specialized rehabilitation in the Southern part of the Netherlands. All participants receive a post-rehabilitation support service. The support service consists of several house visits by a peer support volunteer in the first weeks after specialized rehabilitation treatment. The peer support volunteers are trained according to an adapted version of the previously developed Self-Management Support (SMS) program. The SMS program is directed at improving social and emotional self-management. Patient outcomes are assessed by questionnaire pre-, directly post-, and 6 months post-intervention. The primary patient outcome measure is self-efficacy. Secondary outcomes are perceived autonomy, quality of life, and psychological well-being. A process evaluation will be performed to gain insight into barriers and facilitators for the implementation of peer-led SMS by combining both quantitative, questionnaire data and qualitative data derived from focus groups with peer supporters and patients. In a workshop with relevant stakeholders, possibilities for dissemination and sustainability will be explored. Discussion: This paper describes the design of a practice-based study on feasibility, barriers, and facilitators to the implementation of a home-based, peer-led self-management support intervention for patients with acquired brain injury. We will quantitatively and qualitatively evaluate the change in relevant patient outcomes pre- and post-intervention and the barriers and facilitators related to the implementation of the intervention. Following a positive evaluation, the final stage of the study aims to facilitate deployment and utilization of the intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Baumgartner-Dupuits, Sep, Verbunt, Bosma and van Eijk.)

Background: Recent studies report deficits in social cognition in individuals with multiple sclerosis (MS). Social cognitive skills such as empathy are important for adequate social and occupational functioning. Our objectives are: (1) to examine whether empathy differs between individuals with MS and healthy controls, (2) to examine relations between empathy and cognitive, psychological and occupational functioning., Methods: 278 individuals with MS (relapsing-remitting subtype) and 128 healthy controls from the MS@Work study participated in this investigation. The participants completed questionnaires about demographics, cognitive, psychological and occupational functioning, and underwent neurological and neuropsychological examinations. Mann-Whitney U-tests were used to examine group differences in empathy. Pearson and Spearman rank correlation analyses were used to examine relations between empathy and the other measures., Results: Empathy did not differ between individuals with MS and healthy controls. In individuals with MS, higher empathy was correlated with a higher educational level (X 2 (df) = 13.2(2), p = 0.001), better verbal learning (r = 0.20, p = 0.001), less symptoms of depression (r=-0.21, p = 0.001), higher extraversion (r = 0.25, p ≤ 0.001), agreeableness (r = 0.55, p ≤ 0.001) and conscientiousness (r = 0.27, p ≤ 0.001) and better occupational functioning in terms of work scheduling and output demands (r = 0.23, p = 0.002) and less cognitive/psychological work barriers (r = -0.21, p = 0.001). In healthy controls, higher empathy was correlated with less symptoms of depression (r = -0.34, p ≤ 0.001), less fatigue (r = -0.37, p ≤ 0.001), higher agreeableness (r = 0.59, p ≤ 0.001) and better occupational functioning in terms of work ability as compared to lifetime best (r = 0.28, p = 0.001) and less cognitive/psychological work barriers (r = -0.34, p ≤ 0.001). Empathy did not differ between unemployed and employed individuals with MS or healthy controls., Conclusion: Empathy did not differ between individuals with MS and healthy controls. Within both investigated groups, higher empathy was weakly to moderately correlated with less symptoms of depression, higher agreeableness and better occupational functioning. We also found unique correlations for empathy within the investigated groups. Longitudinal studies are needed to further examine social cognition in relation to cognitive, psychological and occupational functioning in both individuals with MS and healthy controls. It would be particularly interesting to concurrently examine changes in the brain network involved with social cognition., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Multiple sclerosis (MS) is a chronic disorder of the central nervous system with an unpredictable disease course. Life partners often become caregivers, which can be both rewarding and challenging, as the caregiver's physical and mental health is often negatively affected. Previous studies on caregiver strain focused on caregivers of persons with MS with relatively high disability levels, while caregiver strain may already be experienced by life partners living with mildly disabled persons with MS., Objective: The current study examines factors associated with caregiver strain in life partners of persons with mild disability due to relapsing-remitting MS., Methods: We included 173 persons with relapsing-remitting MS (79% female; mean age 42.8 years; 90% employed; median EDSS 2.0) and their life partners. The life partners completed questionnaires on caregiver strain and neuropsychiatric and cognitive functioning of the person with MS. The persons with MS completed questionnaires about demographics, fatigue, personality, physical, cognitive and neuropsychiatric functioning, and underwent neuropsychological and neurological examinations. A linear regression analysis was conducted to examine predictors of caregiver strain., Results: 24% of the life partners experienced above average levels of caregiver strain. A multivariate linear regression analysis revealed that a higher age of the person with MS (β = 0.16, p = 0.04), more physical disability (β = 0.17 p = 0.04), more cognitive and neuropsychiatric problems of the person with MS as reported by the life partner (β = 0.33, p = 0.001) and higher severity of neuropsychiatric symptoms as reported by the life partner (β = 0.32, p = 0.001) were associated with higher caregiver strain (R 2  = 0.49)., Conclusion: Higher caregiver strain in life partners of persons with mild disability due to relapsing-remitting MS was primarily associated with cognitive and neuropsychiatric problems of the person with MS., (Copyright © 2019. Published by Elsevier B.V.)

Background and Objective: Natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) patients may show imaging signs suggestive of inflammation at diagnosis ('inflammatory PML'), reminiscent of PML-immune reconstitution inflammatory syndrome (PML-IRIS). We investigated the imaging characteristics of inflammatory NTZ-PML lesions and PML-IRIS to determine differentiating and overlapping features., Methods: We scored the presence, localisation and pattern of imaging characteristics of inflammation on brain MRI scans of inflammatory NTZ-PML patients. The imaging characteristics were followed up until the occurrence of PML-IRIS., Results: Ten out of the 44 NTZ-PML patients included showed signs suggestive of inflammation at the time of diagnosis. The inflammation pattern at diagnosis was similar to the pattern seen at PML-IRIS, with contrast enhancement representing the most frequent sign of inflammation (90% at diagnosis, 100% at PML-IRIS). However, the severity of inflammation differed, with absence of swelling and low frequency of perilesional oedema (10%) at diagnosis, as compared with the PML-IRIS stage (40%)., Conclusion: Patterns of inflammation at the time of PML diagnosis and at the PML-IRIS stage overlap but differ in their severity of inflammation. This supports histopathological evidence that the inflammation seen at both stages of the same disease shares a similar underlying pathophysiology, representing the immune response to the JC virus to a variable extend., Competing Interests: Competing interests: MPW has received consultancy fees from Biogen, Novartis and Roche. FB serves as a consultant for Bayer-Schering Pharma, Sanofi-Aventis, Biogen, Teva, Novartis, Roche, Synthon BV, Genzyme and Jansen Research. JK has accepted consulting fees from Merck-Serono, TEVA, Biogen, Genzyme and Novartis. BMJU has received consultancy fees from Novartis, Merck Serono, Biogen and Danone Research. MTW does not report any competing interest. The VUmc has received financial support for research activities from Bayer Schering Pharma, Biogen, Glaxo Smith Kline, Merck Serono, Novartis and Teva. JE received consultancy fees and/or lecture fees from Biogen, Genzyme, Teva, Merck and Novartis. The authors had full editorial control of the manuscript and provided their final approval of all content., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The impact of stress on anger and aggression in Borderline Personality Disorder (BPD) and Attention Deficit Hyperactivity Disorder (ADHD) has not been thoroughly investigated. The goal of this study was to investigate different aspects of anger and aggression in patients with these disorders., Methods: Twenty-nine unmedicated female BPD patients, 28 ADHD patients and 30 healthy controls (HC) completed self-reports measuring trait anger, aggression and emotion regulation capacities. A modified version of the Point Subtraction Aggression Paradigm and a state anger measurement were applied under resting and stress conditions. Stress was induced by the Mannheim Multicomponent Stress Test (MMST)., Results: Both patient groups scored significantly higher on all self-report measures compared to HCs. Compared to ADHD patients, BPD patients reported higher trait aggression and hostility, a stronger tendency to express anger when provoked and to direct anger inwardly. Furthermore, BPD patients exhibited higher state anger than HCs and ADHD patients under both conditions and showed a stress-dependent anger increase. At the behavioral level, no significant effects were found. In BPD patients, aggression and anger were positively correlated with emotion regulation deficits., Conclusions: Our findings suggest a significant impact of stress on self-perceived state anger in BPD patients but not on aggressive behavior towards others in females with BPD or ADHD. However, it appears to be pronounced inwardly directed anger which is of clinical importance in BPD patients.

Impulsivity often develops from disturbed inhibitory control, a function mainly regulated by γ-Aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC) and the fronto-striatal system. In this study, we combined MRS GABA measurements and fMRI to investigate neurochemical and neurofunctional correlates of interference inhibition, further emphasizing the direct relationship between those two systems, as well as their relations to impulsivity in patients with BPD. In addition to BOLD activation, task-dependent functional connectivity was assessed by a generalized psychophysiological interactions approach. Full factorial analyses were performed via SPM to examine the main effect (within-group associations) as well as the interaction term (group differences in the association slope). The UPPS scales were used to evaluate impulsivity traits. Compared to healthy controls (HCs), BPD patients exhibited significantly less ACC-caudate functional connectivity during interference inhibition. ACC GABA levels in BPD patients but not in HCs were positively related to the magnitude of activation in several fronto-striatal regions (e.g. ACC, frontal regions, putamen, caudate,) and the strength of ACC-caudate functional connectivity during interference inhibition. The strength of the correlations of GABA with connectivity significantly differs between the two groups. Moreover, among all the UPPS impulsivity subscales, UPPS sensation seeking in the BPD group was related to GABA and was also negatively related to the task-dependent BOLD activation and functional connectivity in the fronto-striatal network. Finally, mediation analyses revealed that the magnitude of activation in the caudate and the strength of ACC-caudate functional connectivity mediated the relationship between ACC GABA levels and UPPS sensation seeking in patients with BPD. Our findings suggest a disconnectivity of the fronto-striatal network in BPD patients during interference inhibition, particularly for patients with higher impulsivity. The ACC GABAergic system seems to play a crucial role in regulating regional BOLD activations and functional connectivity in this network, which are further associated with impulsive sensation seeking in BPD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Both chronic alcohol consumption and alcohol withdrawal lead to neural tissue damage which partly recovers during abstinence. This study investigated withdrawal-associated changes in glutamatergic compounds, markers of neuronal integrity, and gray matter volumes during acute alcohol withdrawal in the hippocampus, a key region in development and maintenance of alcohol dependence in humans and rats., Methods: Alcohol-dependent patients (N = 39) underwent magnetic resonance imaging (MRI) and MR spectroscopy (MRS) measurements within 24 hours after the last drink and after 2 weeks of abstinence. MRI and MRS data of healthy controls (N = 34) were acquired once. Our thorough quality criteria resulted in N = 15 available spectra from the first and of N = 21 from the second measurement in patients, and of N = 19 from healthy controls. In a translational approach, chronic intermittent ethanol-exposed rats and respective controls (8/group) underwent 5 MRS measurements covering baseline, intoxication, 12 and 60 hours of withdrawal, and 3 weeks of abstinence., Results: In both species, higher levels of markers of glutamatergic metabolism were associated with lower gray matter volumes in the hippocampus in early abstinence. Trends of reduced N-acetylaspartate levels during intoxication persisted in patients with severe alcohol withdrawal symptoms over 2 weeks of abstinence. We observed a higher ratio of glutamate to glutamine during alcohol withdrawal in our animal model., Conclusions: Due to limited statistical power, we regard the results as preliminary and discuss them in the framework of the hypothesis of withdrawal-induced hyperglutamatergic neurotoxicity, alcohol-induced neural changes, and training-associated effects of abstinence on hippocampal tissue integrity., (Copyright © 2017 by the Research Society on Alcoholism.)

A 72-year-old woman who recently had been treated with metronidazole presented with subacute dysarthria, gait ataxia and encephalopathy with severe anxiety. Head MRI showed symmetrical T2-hyperintensities. Under suspicion of a metronidazole-induced encephalopathy, metronidazole was stopped immediately. The patient recovered completely and follow-up MRI showed complete resolution of T2-hyperintensities.

Background: Job loss is common in multiple sclerosis (MS) and is known to exert a negative effect on quality of life. The process leading up to job loss typically includes negative work events, productivity losses and a need for accommodations. By using active coping strategies job loss may be prevented or delayed., Objective: Our goal was to examine negative work events and accommodations in relation to coping strategies in employed relapsing-remitting MS patients., Methods: Ninety-seven MS patients (77% females; 21-59 years old) completed questionnaires concerning the patient's work situation, coping strategies, demographics, physical, psychological and cognitive functioning. Forward binary logistic regression analyses were conducted to examine coping strategies and other (disease) characteristics predictive of reported negative work events and accommodations., Results: Nineteen per cent of the employed MS patients reported one or more negative work events, associated with a higher use of emotion-oriented coping and more absenteeism. Seventy-three per cent reported using one or more work accommodations, associated with a higher educational level and more presenteeism. MS patients reporting physical changes to the workplace employed more emotion-oriented coping, while flexible scheduling was associated with task-oriented coping., Conclusion: Emotion-oriented and task-oriented coping strategies are associated with negative work events and the use of accommodations.

We explored brain volume recovery in terms of cortical thickness (CTh; gyral, sulcal pattern) and surface area (SA), as well as subcortical volume recovery in the first 2 weeks of abstinence in 49 alcohol-dependent patients (ADPs). A widespread reduction of CTh in ADPs at day 1 of abstinence compared to healthy controls, with more pronounced differences in sulci relative to gyri was found. After 2 weeks of abstinence, partial recovery to varying degrees of CTh loss in ADPs was observed for several regions. The longitudinal CTh changes were greater in sulci than in gyri of affected regions. No longitudinal change in SAs and subcortical volumes was found. Alterations of CTh contribute to brain volume loss in alcoholism and recovery during early abstinence. Sulci seem to be more vulnerable to excessive alcohol consumption and to drive abstinence-induced volume recovery. During the initial 2 weeks of abstinence no subcortical volume regain was observed. Either the time span was too short or the lower subcortical volume could represent a predisposing trait marker., (© 2015 S. Karger AG, Basel.)

Borderline personality disorder (BPD) and attention-deficit-hyperactivity disorder (ADHD) are both characterized by high impulsivity and difficulties in controlling anger and aggression. In BPD, comorbid ADHD may further increase impulsivity. For both disorders, altered MR spectroscopy levels of the neurotransmitters glutamate and GABA as well as some correlations with impulsivity were previously reported. The objective of this study was to investigate the neurotransmitters glutamate and GABA in relation to impulsivity and aggression as expressed in the anterior cingulate cortex (ACC) in groups of female patients with BPD and ADHD, respectively. Associations of glutamate and GABA levels with further BPD (symptom severity) and ADHD aspects (hyperactivity and inattention) were exploratively evaluated. 1H MR spectra were acquired at 3T to determine glutamate to total creatine ratios (Glu/tCr) and GABA levels from the ACC in a BPD group (n=26), an ADHD group (n=22), and a healthy control (HC) group (n=30); all participants were females. Both patient groups showed higher scores on self-reported impulsivity, anger, and aggression compared with HCs. ACC GABA levels were significantly lower in ADHD than HC. Although measures of impulsivity were positively related to glutamate and negatively to GABA, for aggression only a negative correlation with GABA could be demonstrated. These data provide human in vivo evidence for the role of ACC Glu/tCr and GABA in impulsivity and aggression. If distinct associations of Glu/tCr and GABA for BPD and ADHD can be confirmed in future studies, this might yield implications for more specific pharmacological treatments.

Background: Infection with hepatitis E virus genotype 3 (HEV3) is an emerging zoonosis in the industrialized world. The infection usually proceeds asymptomatically. Extrahepatic sequelae including neurological symptoms have been described., Case Description: A 52-year-old man presented at the emergency department with pain, muscle weakness and sensory disorders in both shoulders and arms. He was found to have bilateral neuralgic amyotrophy accompanying an HEV3 infection., Conclusion: An HEV3 infection can have neurological sequelae, but very little is known about its incidence and spectrum of symptoms.