Low-grade inflammation and metabolic syndrome are seen in many chronic diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). Lifestyle interventions which combine different non-pharmacological therapies have shown synergizing effects in improving outcomes in patients with other chronic diseases or increased risk thereof, especially cardiovascular disease. For RA and metabolic syndrome-associated OA (MSOA), whole food plant-based diets (WFPDs) have shown promising results. A WFPD, however, had not yet been combined with other lifestyle interventions for RA and OA patients. In this protocol paper, we therefore present Plants for Joints, a multidisciplinary lifestyle program, based on a WFPD, exercise, and stress management. The objective is to study the effect of this program on disease activity in patients with RA (randomized controlled trial [RCT] 1), on a risk score for developing RA in patients with anti-citrullinated protein antibody (ACPA) positive arthralgia (RCT 2) and on pain, stiffness, and function in patients with MSOA (RCT 3), all in comparison with usual care.We designed three 16-week observer-blind RCTs with a waiting-list control group for patients with RA with low to moderate disease activity (2.6 ≤ Disease Activity Score [DAS28] ≤ 5.1, RCT 1, n = 80), for patients at risk for RA, defined by ACPA-positive arthralgia (RCT 2, n = 16) and for patients with metabolic syndrome and OA in the knee and/or hip (RCT 3, n = 80). After personal counseling on diet and exercise, participants join 10 group meetings with 6-12 other patients to receive theoretical and practical training on a WFPD, exercise, and stress management, while medication remains unchanged. The waiting-list control group receives usual care, while entering the program after the RCT. Primary outcomes are: difference in mean change between intervention and control groups within 16 weeks for the DAS28 in RA patients (RCT 1), the RA-risk score for ACPA positive arthralgia patients (RCT 2), and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score for MSOA patients (RCT 3). Continued adherence to the lifestyle program is measured in a two-year observational extension study.
Psoriasis (Pso) is a chronic inflammatory skin disease, and up to 30% of Pso patients develop psoriatic arthritis (PsA), which can lead to irreversible joint damage. Early detection of PsA in Pso patients is crucial for timely treatment but difficult for dermatologists to implement. We, therefore, aimed to find disease-specific immune profiles, discriminating Pso from PsA patients, possibly facilitating the correct identification of Pso patients in need of referral to a rheumatology clinic. The phenotypes of peripheral blood immune cells of consecutive Pso and PsA patients were analyzed, and disease-specific immune profiles were identified via a machine learning approach. This approach resulted in a random forest classification model capable of distinguishing PsA from Pso (mean AUC = 0.95). Key PsA-classifying cell subsets selected included increased proportions ofdifferentiated CD4+CD196+CD183-CD194+ and CD4+CD196-CD183-CD194+ T-cells and reduced proportions of CD196+ and CD197+ monocytes, memory CD4+ and CD8+ T-cell subsets and CD4+ regulatory T-cells. Within PsA, joint scores showed an association with memory CD8+CD45RACD197- effector T-cells and CD197+ monocytes. To conclude, through the integration of in-depth flow cytometry and machine learning, we identified an immune cell profile discriminating PsA from Pso. This immune profile may aid in timely diagnosing PsA in Pso.
MULTIFILE
BACKGROUND: Mobile devices such as smartphones and tablets have surged in popularity in recent years, generating numerous possibilities for their use in health care as mobile health (mHealth) tools. One advantage of mHealth is that it can be provided asynchronously, signifying that health care providers and patients are not communicating in real time. The integration of asynchronous mHealth into daily clinical practice might therefore help to make health care more efficient for patients with rheumatoid arthritis (RA). The benefits have been reviewed in various medical conditions, such as diabetes and asthma, with promising results. However, to date, it is unclear what evidence exists for the use of asynchronous mHealth in the field of RA.OBJECTIVE: The objective of this study was to map the different asynchronous mHealth interventions tested in clinical trials in patients with RA and to summarize the effects of the interventions.METHODS: A systematic search of Pubmed, Scopus, Cochrane, and PsycINFO was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies were initially screened and later assessed by two independent researchers. Disagreements on inclusion or exclusion of studies were resolved by discussion.RESULTS: The literature search yielded 1752 abstracts. After deduplication and screening, 10 controlled intervention studies were included. All studies were assessed to be at risk for bias in at least one domain of the Cochrane risk-of-bias tool. In the 10 selected studies, 4 different types of mHealth interventions were used: SMS reminders (to increase medication adherence or physical activity; n=3), web apps (for disease monitoring and/or to provide medical information; n=5), smartphone apps (for disease monitoring; n=1), and pedometers (to increase and track steps; n=1). Measured outcomes varied widely between studies; improvements were seen in terms of medication compliance (SMS reminders), reaching rapid remission (web app), various domains of physical activity (pedometer, SMS reminders, and web apps), patient-physician interaction (web apps), and self-efficacy (smartphone app).CONCLUSIONS: SMS reminders, web apps, smartphone apps, and pedometers have been evaluated in intervention studies in patients with RA. These interventions have been used to monitor patients or to support them in their health behavior. The use of asynchronous mHealth led to desirable outcomes in nearly all studies. However, since all studies were at risk of bias and methods used were very heterogeneous, high-quality research is warranted to corroborate these promising results.
The missing link in diagnostic testing for rheumatoid arthritis (RA) is an agglutination assay, easy to perform and dedicated to decentralized testing. Approximately 75% of RA patients produce autoantibodies to citrullinated proteins (ACPA), which can be detected using an agglutination-based diagnostic test. Such a diagnostic test will be cheaper, less laborious and faster than current tests and does not require sophisticated equipment. Novio Catalpa is developing this alternative test for ACPA in collaboration with Radboud University. To develop this test, specifically tagged and citrullinated nanobodies are needed, but the production is still challenging. Current methods for the production of ACPA diagnostics involve chemical synthesis, in which a variety of toxic chemicals are used in each step. The alternative assay involves nanobodies fused with RA-biomarker target entities, which can be completely produced by ‘green synthesis’ in the yeast Pichia pastoris using the expertise of HAN BioCentre. The yeast P. pastoris has proven to be able to produce nanobodies and is a fast and cost-effective platform that often results in high protein yields. Goal of the project is therefore to determine the feasibility and best green route to produce purified nanobodies tagged with citrullinated ACPA targets that can be used for developing an agglutination assay for RA. P. pastoris does not produce endogenous PAD enzymes which are needed for citrullination of the nanobodies in order to be able to use it in a RA agglutination test. Therefore, PAD enzymes from other sources need to be tested and applied. The project results will be directly used by Novio Catalpa to further develop the innovative test for RA. This project will contribute to and finally result in a single-step agglutination assay suitable for both point-of-care testing and automation in clinical laboratories.
In Europe nearly 10% of the population suffers from diabetes and almost 1% from Rheumatoid Arthritis which can lead to serious problems with mobility and active participation, especially in the ageing population. Pedorthists deliver personalised designed and manufactured orthopaedic footwear or insoles for these patients. However, despite their often laborious efforts upfront, the industry has very little means to quantify how successful the fitting and function of a shoe is. They have to rely on subjective, qualitative measures such as client satisfaction and diminishing of complaints. Although valuable, the need for objective quantitative data in this field is growing. Foot plantar pressure and shear forces are considered major indicators of potential foot problems. Devices to measure plantar pressure slowly gain terrain as providers of objective quantitative data to guide orthotic design and manufacturing. For shear forces however, measuring devices are not yet commercial available. Although shear forces are considered as a major contributor to ulcer formation in diabetic feet, their exact role still requires elucidation and quantification. This project aims to develop a prototype of an in-shoe wearable device that measures both shear forces and pressure using state-of-the-art developments in sensor technologies, smart textiles and wireless data transfer. The collaboration of pedorthists’ small and medium-sized enterprises (SME)’s with medical device engineering companies, knowledge institutes,technical universities and universities of applied sciences in this project will bring together the different fields of expertise required to create an innovative device. It is expected that the tool will be beneficial to improve the quality of pedorthists’ services and potentially reduce health insurance costs. Furthermore, it can be used in new shear forces research and open new business potential. However, the eventual aim is to improve patient care and help maintain personal mobility and participation in society.
