Joint research in regional hospitals New research projects from promotion fund

This year, four research projects have been honored in the promotion fund of the Radboudumc and four regional hospitals. The research projects, which are a collaboration between CWZ, Jeroen Bosch Hospital, Rijnstate, Sint Maartenskliniek and the Radboudumc will collectively receive a contribution of 240,000 euros. 

To encourage cooperation between the regional hospitals, a promotion fund was launched in 2016. From this, the hospitals finance doing joint research. Over the past four years, 23 projects have been funded, of which four PhD candidates have completed their research to date. The next projects will start: 

Suzanne Booij (CWZ) & Rick Helmich (Radboudumc)

Project title: The BAT study: botulinum toxin for arm tremor.

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Arm tremor is the most prevalent movement disorder worldwide. One of the most common underlying disorders is dystonic tremor syndrome, defined as tremor combined with abnormal posturing (dystonia). There are two types: dystonic tremor (DT), where dystonia occurs in the same body part as tremor, and tremor associated with dystonia (TAWD), where dystonia and tremor occur in different body parts. Patients with disabling arm tremor currently undergo trial-and-error treatment with various drugs. However, in >50% of cases, medication is not effective or stopped because of side effects. Deep brain surgery is an invasive alternative for medication-resistant tremor patients, but only very few choose this option. Therefore, new treatments tailored to each patient’s individual tremor characteristics are highly needed.

Botulinum toxin (BTX) injections in tremulous muscles is effective for action tremor. However, a major barrier in bringing this treatment to clinical practice is the difficulty to predict who will benefit from this treatment. This is not trivial: own data indicate a very large inter-individual variability, ranging from 0 to 80% tremor reduction. Here, we will investigate whether clinical, ultrasound, and electrophysiological tremor assessments can help decide who will optimally benefit from BTX, by testing whether the efficacy of BTX depends on the clinical diagnosis and/or on the tremulous muscles. We will include patients with either DT (n=30) or TAWD (n=30), who will each undergo 4 sessions of BTX treatment. Outcomes include clinical and electrophysiological assessments at three time points: (1) baseline, (2) just before the fourth BTX treatment (“OFF-BTX” state), and (3) six weeks after the fourth BTX treatment (“ON-BTX” state), which is ±1 year after baseline. BTX effects on tremor will be compared between clinical groups and as a function of electrophysiological patterns. 

This project will produce: (i) novel scientific evidence on the clinical efficacy of BTX in dystonic tremor syndrome; and (ii) a practical algorithm for neurologists to decide whether BTX is suitable for a patient with action tremor.

Brigitte van der Heijden (Jeroen Bosch Ziekenhuis) &  Ioannis Sechopoulos (Radboudumc)

Project title: Four-dimensional computed tomography (4D CT) imaging of the wrist: Improved diagnostics of wrist joint pathologies.

Post-traumatic instability of the wrist joint (carpus) due to ligament lesions is a common and serious pathology. If left untreated, this will progress to debilitating osteoarthritis, limiting the ability to perform routine daily and work-related tasks, increasing sick leave and unemployment. Since it mainly affects the young working population, both personal and societal impact is high. Therefore, both earlier and less invasive diagnosis is needed, which would drastically decrease societal costs and improve patient care. Unfortunately, imaging early carpal instability requires wrist motion, but all current imaging techniques are static. Wrist arthroscopy is considered the reference standard for diagnosing carpal instability, but it is static, invasive, expensive, and is associated with complications and sick leave. In addition, as recognized by the Dutch Association of Plastic Surgery (NVPC), how to treat this pathology is also still an open question. Current imaging methods and arthroscopy do not provide enough information about the patient condition to be able to personalize treatment.

Therefore, there is an urgent need to evaluate wrists while in motion to enable early and accurate diagnosis of carpal instability. This would lead to an optimized treatment plan for each individual patient, improving patient care and drastically decreasing societal costs. For this, a non-invasive, objective, repeatable, and quantitative diagnostic method that reliably estimates the degree of instability is needed. 

We propose that four-dimensional computed tomography (4DCT) imaging, a non-invasive, dynamic imaging modality that is affordable and takes only a few minutes to perform, is ideally suited to meet this need. In 4DCT, the patient moves the wrists while a series of 3D images is obtained, providing information on wrist kinematics. 
In this project, we will develop, assess, and validate 4DCT for diagnosis and treatment planning of carpal instability. 

Maurits van Meer (Rijnstate) & Heiman Wertheim (Radboudumc)

Project title: Rapid antibiotic resistance tests to improve accurate use of last-resort antibiotics in patients with urinary tract infections.

Antibiotic resistance, especially in gram-negative bacteria, is a major threat to modern medicine, leading to increased failure of treatment, morbidity and mortality. The increase in resistance is driven by high use of last-resort broad-spectrum antibiotics, including carbapenems. At the Emergency Department (ED), where use of antibiotics is high, reduction of unnecessary carbapenems use is important to halt the rise in antibiotic resistance for individual patients and the society.

The reliance on last-resort antibiotics is driven by the inability to predict whether a patient has an infection with an antibiotic resistant bacterium. Traditional culture-based techniques take several days before broad-spectrum therapy can be changed to targeted small-spectrum antibiotics. Patients with complicated urinary tract infections (cUTI) are especially affected by antibiotic resistance and are the most important group of patients at the ED who receive empirical treatment with last-resort antibiotics. Prompt knowledge on the presence or absence of resistance enzymes/genes in urine samples will reduce empirical use of broad-spectrum antibiotics without exposing patients to the risk of undertreatment. 

Our main objective of this project is to give patients with suspected cUTI the appropriate antibiotic treatment with as few last-resort antibiotics as possible without increasing the risk of undertreatment. Rapid antibiotic resistance  tests (RATs) are promising to fulfill this role. However, these tests have not yet been clinically validated and thus cannot be implemented in practice. 

The research aims are 1) to assess the diagnostic value of several RATs on urine specimens of patients with cUTI at the ED, 2) to assess the clinical impact of the best performing RAT on appropriate empirical antibiotic use in patients with cUTI and 3) to assess the uptake of the RAT in clinical practice and reasons for (non-)adherence, identifying best practices for implementation of RATs. The results of this project will contribute to reducing antibiotic resistance in individual patients and the society.

Brenda Groen (Sint Maartenskliniek) & Vivian Weerdesteyn (Radboudumc)

Project title: Games to move: Personalized eHealth intervention to improve physical activity in children and adolescents with intellectual and/or physical disabilities.

Background: Many children and adolescents with physical and/or intellectual disabilities face challenges in reaching sufficient PA levels. This leads to negative health effects across the life span. The current surge of digital solutions for promoting PA (e.g. gaming apps and console-based games (exergames)), offers great potential, but their uptake by children and adolescents with disabilities is surprisingly low. Insight into suitability of commercially-available games for this group and personalized support and coaching is needed. 

Objective: To design and evaluate an intervention for personalized enhancement of PA in children and adolescents with disabilities attending special needs education using commercially-available exergames.
Methods: In WP1, the PhD student will perform a needs assessment and inventory of existing exergames resulting in a toolbox with categorized exergames in order to match the wishes and needs of end-users. In WP2, the intervention (including a personalized coaching strategy) will be designed and feasibility will be assessed. In WP3, the effect of the intervention on PA will be evaluated in a proof-of-concept study using a pre-post design (n=50). All steps will be performed in close collaboration with the target group and other stakeholders using patient research partners and an advisory board. 

Expected outcome: This project results in a PhD thesis including 4 published papers, and a low-cost intervention that, when proven effective, can be implemented throughout the Netherlands. 
Impact: This project is highly supported by stakeholders in the field. Enhancing PA will provide obvious health benefits for the 60,000 children/adolescents with disabilities attending special needs education in the Netherlands. Additionally, the proposed approach could serve as a blueprint for other vulnerable groups.
Study team: This new collaboration between the Sint Maartenskliniek and the Radboudumc connects researchers with experience in PA, eHealth and inclusive research with the target population (e.g. Maartenschool, academic collaborative ‘Sterker op eigen benen’). The current surge of digital solutions for promoting PA (e.g. gaming apps and console-based games (exergames)), offers great potential, but their uptake by children and adolescents with disabilities is surprisingly low. Insight into suitability of commercially-available games for this group and personalized support and coaching is needed. 

Study team: This new collaboration between the Sint Maartenskliniek and the Radboudumc connects researchers with experience in PA, eHealth and inclusive research with the target population (e.g. Maartenschool, academic collaborative ‘Sterker op eigen benen’).