Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Monitored natural attenuation (MNA) of contaminated soils: state of the art in Europe – a critical evaluation

The use of natural attenuation (NA) processes for contaminated site cleanup and remediation has been gaining more attention over the last few years. However, the need for an inventory of the existing information concerning monitored natural attenuation (MNA), including the existing return on experience, has been sounding increasingly louder over recent years as well. This paper will focus on the application of MNA throughout Europe. First, a literature study and survey was performed in order to collect all available data on both qualitative and quantitative aspects of MNA. Secondly, a questionnaire was created and sent out to experts in the field of regulation and research from six countries, including Finland, Spain, and the UK. Thirdly, further contributions from a SNOWMAN workshop concerning MNA were included in this paper. The result is a state of the art concerning MNA for several countries, including the legal framework and existing protocols, a comparison between different countries, and an overview of some existing MNA cases throughout Europe combined with a discussion on relevant aspects related to ”return on experience”. The results demonstrate that MNA is now considered to be a conventional remediation technique in most countries that were included in this study. Although MNA is currently being applied for the remediation of contaminated sites, some countries still don’t recognize it as an official remediation technique (e.g. Finland). This study also confirms and illustrates the differences concerning the MNA approach that exist between different countries, as well as the differences in application levels. However, it is important to note that at the same time a certain level of coherence exists concerning the MNA approach, e.g. with regard to the importance of biodegradation processes. Furthermore, the main outcome of this study emphasizes the clear need to systematically collect and share information concerning existing MNA cases. Only then a clear return of experience will be possible.status: publishe

Purpura thrombotique thrombocytopenique fulminant au decours d'un traitement par ciprofloxacine

Nous rapportons un cas de purpura thrombotique thrombocytopénique (PTT) fulminant, survenu au décours d'un traitement par ciprofloxacine chez une patiente âgée de 43 ans. Une méningo-encéphalite bactérienne aiguë avec coagulation intravasculaire disséminée fut d'abord suspectée. La patiente présentait une anémie hémolytique et une thrombopénie sévère empêchant la réalisation immédiate d'une ponction lombaire. Celle-ci ne fut réalisée qu'après transfusion de plaquettes sanguines et permettait d'exclure une méningo-encéphalite. Le diagnostic de PTT fut posé et la patiente fut traitée par plasmapherèses. Cependant, son état neurologique s'aggrava avec apparition au scanner X crânien d'une hémorragie sous-arachnoïdienne sylvienne gauche, d'un oedème cérébral diffus prédominant à l'hémisphère gauche et de lacunes ischémiques disséminées. Elle décéda quatre jours après l'admissio

SHIFTPLAN : a randomized controlled trial investigating the effects of a multimodal shift-work intervention on drivers\u2019 fatigue, sleep, health, and performance parameters

BACKGROUND: Shift work is commonly associated with health problems resulting from circadian misalignment and sleep restriction. About one in three shift workers is affected by insomnia and up to 90% report regular fatigue and/or sleepiness at the workplace. Epidemiological data shows that shift workers are at increased risk of cardiovascular disease, diabetes, obesity, breast cancer, mental-health problems, and shift-work disorder, which conditions typically lead to reduced work performance, processing errors, accidents at work, absenteeism, and reduced quality of life. Given these widespread and debilitating consequences, there is an urgent need for treatments that help improve the sleep, health, and functional performance of the shift-working population. The most common non-pharmacological recommendations are improved scheduling, bright-light exposure, napping, psychoeducation promoting sleep hygiene, and cognitive-behavioral techniques. The objectives of the present study are to investigate the effects of a multimodal shift-work intervention on perceived fatigue, sleepiness, physical and mental health, sleep parameters, and absenteeism. METHODS: A randomized controlled interventional study comparing the two groups each comprising at least 80 drivers of a public transport company, using self-report questionnaires and health checks completed at intake and after 3 and 6 months following the start of the intervention or waiting-list period. The intervention consists of (a) healthy scheduling taking into account shift-rotation direction and speed, chronotype, resting time, and napping; (b) an education program specifically developed for shift workers; and (c) a dedicated information campaign for shift planners. The primary outcome is symptomatic burden in terms of sleepiness, and the key secondary outcome is symptomatic burden in terms of fatigue. Supplementary secondary outcomes are sleep parameters, absenteeism, general and clinical health, changes in mood, and anxiety. DISCUSSION: Expected outcomes are significant improvements on all primary and secondary outcome parameters in the intervention group. To our knowledge, ours is the first randomized controlled study to systematically investigate the effects of a multimodal program on multiple health, sleep, and performance parameters in shift workers. Our research also aims at providing evidence-based practice guidelines for healthy scheduling in general and thus contribute to diminishing the serious health and economic burdens associated with shift work overall. TRIAL REGISTRATION: EDGE registration number: 000339. ClinicalTrials.gov NCT05452096 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06573-6

Student participation as a strategy for transformative learning

Goals: 1) Provide an overview of the organization of student participation at Ghent University; 2) The achievements of student participation in our curriculum in relation to the concepts of “transformative learning”; 3) Develop an interactive reflection with the participants on student participation; and 4) Provide a framework on how to organize student participation at your faculty. Skills area: The education of health professionals has evolved over the last decennia, a third generation reform imposes itself. Transformative learning, which is about developing leadership attributes, is a key feature in this reform. At Ghent University, the SWME (Student Workgroup of Medical Education) was founded and students began to have a say in the decision making process of the different policy bodies in the faculty (the Educational Committee, the Faculty Council,…). The SWME acts as a change agent, together with health professionals, by continuous review and suggestions for improvement of our curriculum. In the reform of the medicine studies in Belgium from a seven to six-year program, SWME played a big role in the changes of the current curriculum. SWME also encouraged student participation in all the training programs of the faculty (not only in medicine). Another example of student projects is Hercules, a searchable database of all course material of our curriculum at the faculty of Medicine, which will allow a critical review of our course material. Methods: 1) Short overview of the organization SWME; 2) How to motivate peer students to participate within student representation: what are the big difficulties?; 3) Short synopsis of our major projects: SWME-star, SWME-report etc; and 4) Hercules: illustration of the database with an example. Overview: 1)How is student participation organized within the discipline of Medicine of the University of Ghent?; 2) What can we achieve through this?; 3) What are the obstacles you go through?; 4) Presentation of Hercules; and 5) General discussion and conclusions

Barriers to nonpharmacologic treatments for stress, anxiety, and insomnia: Family physicians’ attitudes toward benzodiazepine prescribing

OBJECTIVE: To explore the attitudes of FPs toward benzodiazepine (BZD) prescribing and the perceived barriers to nonpharmacologic approaches to managing stress, anxiety, and insomnia. DESIGN: A questionnaire including 32 statements about treatment of insomnia, stress, and anxiety. SETTING: Local quality groups for FPs in Belgium. PARTICIPANTS: A total of 948 Belgian FPs. MAIN OUTCOME MEASURES: Barriers to using nonpharmacologic approaches in family practice. RESULTS: We identified 3 different groups of FPs according to their attitudes about BZD prescribing. A first relatively big group of FPs (39%) were not really concerned about the risks of BZD prescribing. Those in the second group (17%) were aware of the problems associated with BZDs, but did not perceive it to be their role to use nonpharmacologic approaches in family practice. Those in the third group (44%) were concerned about BZD prescribing and found it to be a "bad solution," but were faced with various barriers to applying nonpharmacologic approaches. Surprisingly, we found that nearly 97% of FPs thought that most people were eligible for nonpharmacologic approaches, but experienced implementation barriers at the level of the patient, the level of the FP, and the level of the health care system. CONCLUSION: Using different education and behavioural-change strategies for different FP groups seems important. A large group of FPs does not find prescribing BZDs to be problematic. Sensitizing and alerting FPs to this issue remains very important.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Effectieve gemeenschapsgerichte zorg in Vlaanderen

status: publishe

Four cases of omental herniation in cattle

Four cases in cattle of omental herniation through an acquired omental rent are described. Clinical signs were indistinguishable from other causes of mechanical ileus and exploratory laparotomy was necessary to establish a diagnosis. In all cases a variably sized portion of jejunal loops was obstructed in an omental rent in the deep layer of the greater omentum. In two cases simple reduction was possible, and in one case incision of the hernial ring was necessary before reduction could be performed. Resection was necessary only in a calf, in which the incarceration was complicated by severe abomasal distension and local peritonitis. In all four cases the omental rent was closed by a serosa-serosa suture. Three cases made an uneventful recovery and returned to normal production, but one of these animals died three months postoperatively from an unknown cause. The calf was euthanased two days postoperatively because of persistent ileus