BackgroundFluid therapy is a common intervention in critically ill patients. It is increasingly recognised that deresuscitation is an essential part of fluid therapy and delayed deresuscitation is associated with longer invasive ventilation and length of intensive care unit (ICU) stay. However, optimal timing and rate of deresuscitation remain unclear. Lung ultrasound (LUS) may be used to identify fluid overload. We hypothesise that daily LUS-guided deresuscitation is superior to deresuscitation without LUS in critically ill patients expected to undergo invasive ventilation for more than 24 h in terms of ventilator free-days and being alive at day 28.MethodsThe “effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients” (CONFIDENCE) is a national, multicentre, open-label, randomised controlled trial (RCT) in adult critically ill patients that are expected to be invasively ventilated for at least 24 h. Patients with conditions that preclude a negative fluid balance or LUS examination are excluded. CONFIDENCE will operate in 10 ICUs in the Netherlands and enrol 1000 patients. After hemodynamic stabilisation, patients assigned to the intervention will receive daily LUS with fluid balance recommendations. Subjects in the control arm are deresuscitated at the physician’s discretion without the use of LUS. The primary endpoint is the number of ventilator-free days and being alive at day 28. Secondary endpoints include the duration of invasive ventilation; 28-day mortality; 90-day mortality; ICU, in hospital and total length of stay; cumulative fluid balance on days 1–7 after randomisation and on days 1–7 after start of LUS examination; mean serum lactate on days 1–7; the incidence of reintubations, chest drain placement, atrial fibrillation, kidney injury (KDIGO stadium ≥ 2) and hypernatremia; the use of invasive hemodynamic monitoring, and chest-X-ray; and quality of life at day 28.DiscussionThe CONFIDENCE trial is the first RCT comparing the effect of LUS-guided deresuscitation to routine care in invasively ventilated ICU patients. If proven effective, LUS-guided deresuscitation could improve outcomes in some of the most vulnerable and resource-intensive patients in a manner that is non-invasive, easy to perform, and well-implementable.Trial registrationClinicalTrials.gov NCT05188092. Registered since January 12, 2022
MULTIFILE
Purpose: To evaluate the effects of a combination of wheelchair mobility skills (WMS) training and exercise training on physical activity (PA), WMS, confidence in wheelchair mobility, and physical fitness. Methods: Youth using a manual wheelchair (n = 60) participated in this practice-based intervention, with a waiting list period (16 weeks), exercise training (8 weeks), WMS training (8 weeks), and follow-up (16 weeks). Repeated measures included: PA (Activ8), WMS (Utrecht Pediatric Wheelchair Mobility Skills Test), confidence in wheelchair mobility (Wheelchair Mobility Confidence Scale), and physical fitness (cardiorespiratory fitness, (an)aerobic performance) and were analysed per outcome parameter using a multilevel model analyses. Differences between the waiting list and training period were determined with an unpaired sample t-test. Results: Multilevel model analysis showed significant positive effects for PA (p = 0.01), WMS (p < 0.001), confidence in wheelchair mobility (p < 0.001), aerobic (p < 0.001), and anaerobic performance (p < 0.001). Unpaired sample t-tests underscored these effects for PA (p < 0.01) and WMS (p < 0.001). There were no effects on cardiorespiratory fitness. The order of training (exercise before WMS) had a significant effect on confidence in wheelchair mobility. Conclusions: A combination of exercise and WMS training appears to have significant positive long-term effects on PA, WMS, confidence in wheelchair mobility, and (an)aerobic performance in youth using a manual wheelchair.Implications for rehabilitationExercise training and wheelchair mobility skills (WMS) training can lead to a sustained improvement in physical activity (PA) in youth using a manual wheelchair.These combined trainings can also lead to a sustained increase in WMS, confidence in wheelchair mobility, and (an)aerobic performance.More attention is needed in clinical practice and in research towards improving PA in youth using a manual wheelchair.
Background: Adverse outcome pathway (AOP) networks are versatile tools in toxicology and risk assessment that capture and visualize mechanisms driving toxicity originating from various data sources. They share a common structure consisting of a set of molecular initiating events and key events, connected by key event relationships, leading to the actual adverse outcome. AOP networks are to be considered living documents that should be frequently updated by feeding in new data. Such iterative optimization exercises are typically done manually, which not only is a time-consuming effort, but also bears the risk of overlooking critical data. The present study introduces a novel approach for AOP network optimization of a previously published AOP network on chemical-induced cholestasis using artificial intelligence to facilitate automated data collection followed by subsequent quantitative confidence assessment of molecular initiating events, key events, and key event relationships. Methods: Artificial intelligence-assisted data collection was performed by means of the free web platform Sysrev. Confidence levels of the tailored Bradford-Hill criteria were quantified for the purpose of weight-of-evidence assessment of the optimized AOP network. Scores were calculated for biological plausibility, empirical evidence, and essentiality, and were integrated into a total key event relationship confidence value. The optimized AOP network was visualized using Cytoscape with the node size representing the incidence of the key event and the edge size indicating the total confidence in the key event relationship. Results: This resulted in the identification of 38 and 135 unique key events and key event relationships, respectively. Transporter changes was the key event with the highest incidence, and formed the most confident key event relationship with the adverse outcome, cholestasis. Other important key events present in the AOP network include: nuclear receptor changes, intracellular bile acid accumulation, bile acid synthesis changes, oxidative stress, inflammation and apoptosis. Conclusions: This process led to the creation of an extensively informative AOP network focused on chemical-induced cholestasis. This optimized AOP network may serve as a mechanistic compass for the development of a battery of in vitro assays to reliably predict chemical-induced cholestatic injury.
Alcohol use disorder (AUD) is a pattern of alcohol use that involves having trouble controlling drinking behaviour, even when it causes health issues (addiction) or problems functioning in daily (social and professional) life. Moreover, festivals are a common place where large crowds of festival-goers experience challenges refusing or controlling alcohol and substance use. Studies have shown that interventions at festivals are still very problematic. ARise is the first project that wants to help prevent AUD at festivals using Augmented Reality (AR) as a tool to help people, particular festival visitors, to say no to alcohol (and other substances). ARise is based on the on the first Augmented Reality Exposure Therapy (ARET) in the world that we developed for clinical treatment of AUD. It is an AR smartphone driven application in which (potential) visitors are confronted with virtual humans that will try to seduce the user to accept an alcoholic beverage. These virtual humans are projected in the real physical context (of a festival), using innovative AR glasses. Using intuitive phone, voice and gesture interactions, it allows users to personalize the safe experience by choosing different drinks and virtual humans with different looks and levels of realism. ARET has been successfully developed and tested on (former) AUD patients within a clinical setting. Research with patients and healthcare specialists revealed the wish to further develop ARET as a prevention tool to reach people before being diagnosed with AUD and to extend the application for other substances (smoking and pills). In this project, festival visitors will experience ARise and provide feedback on the following topics: (a) experience, (b) awareness and confidence to refuse alcohol drinks, (c) intention to use ARise, (d) usability & efficiency (the level of realism needed), and (e) ideas on how to extend ARise with new substances.
The anterior cruciate ligament (ACL) is a strong rope-like tissue which connects the femur to the tibia in the knee joint. Its function is to provide structural stability to the knee while preventing unnatural forward movement of the tibia relative to the femur. Acute complete ACL ruptures during movements like knee hyperextension or sudden changes of direction (pivoting) damage two entities: the ligament itself and its nerve connections to the posterior tibial nerve (PTN). PTN innervation in the ACL is essential for: a) proprioception (e.g. perception of position and movement/acceleration experienced by the ligament), and b) stability of the knee joint. Upon ACL rupture, the orthopedic surgeon reconstructs the ACL with a graft from the hamstring, patellar or quadriceps tendon. After the surgery, the goal is to regain neuromuscular control and dynamic stabilization during rehabilitation as soon as possible for a quick return to sports and daily activities. However, surgeons are not able to reconstruct the nerve gap between the PTN and the grafted ligament due to the microscopic size of the innervation in the ACL. Not linking the PTN to the graft creates a disconnection between the knee joint and the spinal cord. To mitigate these disadvantages in ACL surgery, this study focuses on activating the growth of proprioception nerve endings using a ligament loaded with growth factors (neurotrophins). We hypothesize that neurotrophins will activate proprioceptive fibers of neurons close to the ACL. We describe graft fabrication steps and in vitro experiments to expand on the regeneration capacity of a commercially available ACL-like synthetic ligament called LARS. The results will bring the ACL regeneration field closer to having a graft that can aid patients in regaining mobility and stability during locomotion and running, confidence in the strength of the knee joint, and quick return to sports.
Kinderen van ouders met psychische problemen of verslavingsproblemen (KOPP/KOV) ervaren vaak chronische stress, mentale en lichamelijke gezondheidsproblemen. Ook hun financiële situatie, sociale welzijn en studiesucces kunnen worden beïnvloed door het leven met ouders met psychische en/of verslavingsproblematiek. Vaak zijn zij niet in beeld bij professionals of krijgen alleen verbale therapieën, zoals cognitieve gedragstherapie, terwijl lichaamsgerichte activiteiten geschikter lijken voor mensen die niet makkelijk over gevoelens praten. Sport en bewegen worden weinig ingezet in preventieve en behandelprogramma’s voor KOPP/KOV, alhoewel sport en bewegen positief zijn geassocieerd met gezondheid en welzijn. Boksen heeft aantrekkingskracht op jongeren in kwetsbare posities, heeft de potentie om het zelfvertrouwen, de persoonlijke groei en mentale gezondheid van KOPP/KOV te bevorderen en victimisatie te voorkomen of beperken. Voorwaarde is dat de manier waarop, en context waarin, het boksen wordt aangeboden zijn afgestemd op de wensen, behoeften en mogelijkheden van de doelgroep. Vanuit boks-, sport-, welzijns- en zorgprofessionals is er op dit moment een duidelijke vraag maar ook discussie over de manier waarop boksen ingezet kan worden als adequate preventieve interventie voor KOPP/KOV. Om deze handelingsverlegenheid weg te nemen, vragen bokstrainers maar ook buurtsportcoaches, welzijns- en zorgprofessionals om hulp bij het komen tot een passende en veilige boksinterventie die de mentale gezondheid van KOPP/KOV bevordert. Vanuit ondernemers perspectief zijn er daarnaast ook vragen rondom financiering en scholing van de trainers. Met een ontwerpgerichte aanpak wordt in dit project de volgende onderzoeksvraag beantwoord: “Aan welke inhoudelijke en organisatorische criteria moet een boksinterventie ter bevordering van de mentale gezondheid van KOPP/KOVV in de leeftijd 16-24 jaar voldoen?”. Het beantwoorden van deze vraag zal resulteren in een boksinterventie die kan worden aangeboden in samenwerking tussen ondernemers binnen de boks- en sportwereld én welzijns- en zorgprofessionals, en inzicht geven in de werkzame elementen, bruikbaarheid en haalbaarheid van deze lichaamsgerichte interventie voor KOPP/KOV.
