Objective To compare clinical and patient-reported outcomes (PROs) over 5 years between patients with rheumatoid arthritis (RA) in sustained remission (sREM), sustained low disease activity (sLDA)... Show moreObjective To compare clinical and patient-reported outcomes (PROs) over 5 years between patients with rheumatoid arthritis (RA) in sustained remission (sREM), sustained low disease activity (sLDA) or active disease (AD) in the first year after diagnosis. Methods All patients with RA from the treatment in the Rotterdam Early Arthritis CoHort trial, a multicentre, stratified, single-blinded trial with a treat-to-target approach, aiming for LDA (Disease Activity Score (DAS) ≤2.4), were studied. Patients were categorised into: (1) sREM (mean DAS from 6 to 12 months 2.4) (n=59). Pain, fatigue, functional impairment, health-related quality of life (HRQoL), health status and productivity loss during 5 years were compared between groups. Radiographic progression (modified Total Sharp Score (mTSS)) was compared over 2 years. Results Patients in sLDA in the first year had worse PROs during follow-up, compared with patients in sREM: pain (0–10 Likert) was 0.90 units higher (95% CI 0.52 to 1.27), fatigue (Visual Analogue Scale) was 12.10 units higher (95% CI 7.27 to 16.92), functional impairment (Health Assessment Questionnaire— Disability Index) was 0.28 units higher (95% CI 0.17 to 0.39), physical HRQoL (36-item Short Form Health Survey (SF-36) Physical Component Summary score) was 4.42 units lower (95% CI −6.39 to –2.45), mental HRQoL (SF-36 Mental Component Summary score (MCS)) was 2.95 units lower (95% CI −4.83 to –1.07), health status (European Quality of life 5-Dimensions 3-Levels (EQ-5D-3L)) was 0.06 units lower (95% CI −0.09 to –0.03) and productivity loss (0%–100%) was 7.76% higher (95% CI 2.76 to 12.75). Differences between the AD and sREM group were even larger, except for the SF-36 MCS and EQ5D-3L. No differences in mTSS were found between groups. Conclusion Patients with RA who reach sREM in the first year have better HRQoL and function, and less pain, fatigue and productivity loss in the years thereafter, compared with patients with RA who are in sLDA or AD in the first year. Show less
Objectives To investigate whether there is a window of opportunity for psoriatic arthritis (PsA) patients and to assess which patient characteristics are associated with a longer diagnostic delay.... Show moreObjectives To investigate whether there is a window of opportunity for psoriatic arthritis (PsA) patients and to assess which patient characteristics are associated with a longer diagnostic delay. Methods All newly diagnosed, disease-modifying antirheumatic drug-naïve PsA patients who participated in the Dutch southwest Early PsA cohoRt and had ≥3 years of follow-up were studied. First, total delay was calculated as the time period between symptom onset and PsA diagnosis made by a rheumatologist and then split into patient and physician delays. The total delay was categorised into short (1 year). These groups were compared on clinical (Minimal Disease Activity (MDA) and Disease Activity index for PSoriatic Arthritis (DAPSA) remission) and patientreported outcomes during 3 years follow-up. Results 708 PsA patients were studied of whom 136 (19%), 237 (33%) and 335 (47%) had a short, intermediate and long total delay, respectively. Patient delay was 1.0month and physician delay was 4.5 months. Patients with a short delay were more likely to achieve MDA (OR 2.55, p=0.003) and DAPSA remission (OR 2.35,p=0.004) compared with PsA patients with a long delay. Patientreported outcomes showed numerical but non-significant differences between the short and long delay groups. Female patients and those presenting with enthesitis, chronic back pain or normal C-reactive protein (CRP) had a longer delay. Conclusions In PsA, referral and diagnosis within 1 year is associated with better clinical outcomes, suggesting the presence of a window of opportunity. The most gain in referral could be obtained in physician delay and in females, patients with enthesitis, chronic back pain or normal CRP Show less
Objective: To compare patient-reported outcomes (PROs) from the first year to the third year between patients with psoriatic arthritis (PsA) who achieved minimal disease activity (MDA) in the first... Show moreObjective: To compare patient-reported outcomes (PROs) from the first year to the third year between patients with psoriatic arthritis (PsA) who achieved minimal disease activity (MDA) in the first year after diagnosis and those who did not. Methods:Consecutive, newly diagnosed, patients with DMARD naive PsA with oligoarthritis or polyarthritis were selected from the Dutch southwest Early PsA cohoRt. Patients were categorised in three groups: (1) Patients who were in MDA at both 9 months and 12 months after diagnosis (sustained MDA); (2) Patients who achieved MDA in the first year but in whom it was not sustained at both 9 months and 12 months (non-sustained MDA); (3) Patients who did not achieve MDA in the first year (no MDA). PROs were compared between groups from the first year to the third year after diagnosis using a linear mixed model. Results: 240 patients were selected; 104 (43%) were classified as sustained MDA, 60 (25%) as non-sustained MDA and 76 (32%) as no MDA. Patients who did not achieve MDA in the first year experienced remarkably lower PROs during follow-up, compared with the sustained MDA group: health status (European Quality of life 5-Dimensions 5-Levels) was 0.23 units lower (95% CI -0.28 to -0.18), functional impairment (Health Assessment Questionnaire-Disability Index) was 0.81 units higher (95% CI 0.70 to 0.92), pain (Visual Analogue Scale) was 35.38 mm higher (95% CI 30.57 to 40.18), fatigue (Bristol Rheumatoid Arthritis Fatigue-Multidimensional Questionnaire) was 17.88 units higher (95% CI 14.60 to 21.16), and anxiety and depression (Hospital Anxiety and Depression Scale) were, respectively, 3.26 units (95% CI 2.25 to 4.27) and 4.04 units higher (95% CI 3.10 to 4.99). Conclusion: Failure to achieve MDA in the first year after PsA diagnosis was associated with worse PROs that persisted over the years. Show less
Tuerlings, M.; Boone, I.; Amirabadi, H.E.; Vis, M.; Suchiman, E.; Linden, E. van der; ... ; Meulenbelt, I. 2022
Given the multi-tissue aspects of osteoarthritis (OA) pathophysiology, translation of OA susceptibility genes towards underlying biological mechanism and eventually drug target discovery requires... Show moreGiven the multi-tissue aspects of osteoarthritis (OA) pathophysiology, translation of OA susceptibility genes towards underlying biological mechanism and eventually drug target discovery requires appropriate human in vitro OA models that incorporate both functional bone and cartilage tissue units. Therefore, a microfluidic chip is developed with an integrated fibrous polycaprolactone matrix in which neo-bone and cartilage are produced, that could serve as a tailored human in vitro disease model of the osteochondral unit of joints. The model enables to evaluate OA-related environmental perturbations to (individual) tissue units by controlling environmental cues, for example by adding biochemical agents. After establishing the co-culture in the system, a layer of cartilaginous matrix is deposited in the chondrogenic compartment, while a bone-like matrix is deposited between the fibers, indicated by both histology and gene expression levels of collagen type 2 and osteopontin, respectively. As proof-of-principle, the bone and cartilaginous tissue are exposed to active thyroid hormone, creating an OA disease model. This results in increased expression levels of hypertrophy markers integrin-binding sialoprotein and alkaline phosphatase in both cartilage and bone, as expected. Altogether, this model could contribute to enhanced translation from OA risk genes towards novel OA therapies. Show less
IMPORTANCE Intra-articular (IA) glucocorticoid injection is widely used in patients with knee osteoarthritis (OA), but the safety of this technique is in question among physicians. Intramuscular ... Show moreIMPORTANCE Intra-articular (IA) glucocorticoid injection is widely used in patients with knee osteoarthritis (OA), but the safety of this technique is in question among physicians. Intramuscular (IM) glucocorticoid injection could be an alternative approach.OBJECTIVE To investigate whether an IM glucocorticoid injection is noninferior to an IA glucocorticoid injection in reducing knee pain for patients with knee OA in primary care.DESIGN, SETTING, AND PARTICIPANTS The KIS trial, a multicenter, open-label, randomized clinical noninferiority trial including patients with symptomatic knee OA, was conducted in 80 primary care general practices in the southwest of the Netherlands. The study was conducted from March 1, 2018, to July 28, 2020.INTERVENTIONS Patients were randomly allocated to receive an injection of triamcinolone acetonide, 40 mg, either IM in the ipsilateral ventrogluteal region or IA in the knee joint. All patients were followed up for 24 weeks.MAIN OUTCOMES AND MEASURES The pain score at 4 weeks measured with Knee Injury and Osteoarthritis Outcome Score (range, 0-100; 0 indicates extreme pain), with a noninferiority margin of -7 (IM minus IA). A per-protocol analysis was prespecified as the primary analysis.RESULTS A total of 145 patients (94 women [65%]; mean [SD] age, 67 [10] years) were included; of these, 138 patients (IM, 72; IA, 66) were included in the per-protocol analysis. Clinically relevant improvements in knee pain were reached up to 12 weeks after the injection in both groups. At 4 weeks, the estimated mean difference in the Knee Injury and Osteoarthritis Outcome Score between the 2 groups was -3.4 (95% CI, -10.1to 3.3). Noninferiority could not be declared because the lower limit exceeded the noninferiority margin. Intramuscular injection was noninferior to IA injection at 8 (mean difference, 0.7; 95% CI, -6.5 to 7.8) and 24 (mean difference, 1.6; 95% CI, -5.7 to 9.0) weeks. No significant difference was found among all the secondary outcomes. These results were similar for the sensitivity analysis in an intention-to-treat population. The most frequently reported adverse events were hot flush (IM, 7 [10%] vs IA, 14 [21%]) and headache (IM, 10 [14%] vs IA, 12 [18%]), and all events were classified as nonserious.CONCLUSIONS AND RELEVANCE Based on the findings of this trial, among patients with knee OA in primary care, IM glucocorticoid injection could present an inferior effect in reducing pain at 4 weeks compared with IA injection. Noninferiority of an IM injection was observed at 8 and 24 weeks after injection. This trial provides data for shared decision-making, taking into account the advantages and disadvantages of both types of injections. Show less
Background Despite the availability of guidelines for the performance of transcatheter aortic valve implantation (TAVI), current treatment pathways vary between countries and institutions, which... Show moreBackground Despite the availability of guidelines for the performance of transcatheter aortic valve implantation (TAVI), current treatment pathways vary between countries and institutions, which impact on the mean duration of postprocedure hospitalization.Methods and Results This was a prospective, multicenter registry of 502 patients to validate the appropriateness of discharge timing after transfemoral TAVI, using prespecified risk criteria from FAST-TAVI (Feasibility and Safety of Early Discharge After Transfemoral [TF] Transcatheter Aortic Valve Implantation), based on hospital events within 1-year after discharge. The end point-a composite of all-cause mortality, vascular access-related complications, permanent pacemaker implantation, stroke, cardiac rehospitalization, kidney failure, and major bleeding-was reached in 27.0% of patients (95% CI, 23.3-31.2) within 1 year after intervention; 7.5% (95% CI, 5.5-10.2) had in-hospital complications before discharge and 19.6% (95% CI, 16.3-23.4) within 1 year after discharge. Overall mortality within 1 year after discharge was 7.3% and rates of cardiac rehospitalization 13.5%, permanent pacemaker implantation 4.2%, any stroke 1.8%, vascular-access-related complications 0.7%, life-threatening bleeding 0.7%, and kidney failure 0.4%. Composite events within 1 year after discharge were observed in 18.8% and 24.3% of patients with low risk of complications/early (<= 3 days) discharge and high risk and discharged late (>3 days) (concordant discharge), respectively. Event rate in patients with discordant discharge was 14.3% with low risk but discharged late and increased to 50.0% in patients with high risk but discharged in <= 3 days.Conclusions The FAST-TAVI risk assessment provides a tool for appropriate, risk-based discharge that was validated with the 1-year event rate after transfemoral TAVI.Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02404467. Show less
Background The knee is symptomatically the most frequent affected joint in osteoarthritis and, in the Netherlands and other Western countries, is mainly managed by general practitioners (GPs). An... Show moreBackground The knee is symptomatically the most frequent affected joint in osteoarthritis and, in the Netherlands and other Western countries, is mainly managed by general practitioners (GPs). An intra-articular glucocorticoid injection is recommended in (inter) national guidelines for patients with knee osteoarthritis as an option for a flare of knee pain and/or for those who are not responding well to pain medication. An innovative approach that could replace the intra-articular injection is an intramuscular gluteal glucocorticoid injection. An intramuscular injection is easier to perform than an intra-articular injection with lesser risk of severe local adverse reactions. We hypothesize that intramuscular gluteal glucocorticoid injection is non-inferior in reducing knee pain compared to intra-articular glucocorticoid injection, with potentially a longer lasting effect than intra-articular injection. Methods/design The study will be a pragmatic randomized controlled non-inferiority trial with two parallel groups. A total of 140 patients aged 45 years and older with knee osteoarthritis who contacted their general practitioner and have persistent knee pain (score >= 3 on 0-10 numerical rating scale; 0 = no knee pain) will be included. Patients will be randomly allocated (1:1) to an injection of 40 mg triamcinolone acetonide intra-articular in the knee joint or intramuscular in the ipsilateral ventrogluteal area. The effect of treatment will be evaluated by questionnaires at 2, 4, 8, 12, and 24 weeks after injection. The primary outcome is patients' reported severity of knee pain measured with the pain subscale of the Knee injury and Osteoarthritis Outcome Score 4 weeks after injection. Statistical analysis will be based on both the per-protocol and the intention-to-treat principle. Discussion This study will evaluate non-inferiority of intramuscular glucocorticoid injection compared to intra-articular glucocorticoid injection for knee osteoarthritis symptoms. Trial sponsor Erasmus MC University Medical Center Rotterdam. PO-box 2040. 3000 CA Rotterdam. The Netherlands. Show less
Barbanti, M.; Mourik, M.S. van; Spence, M.S.; Iacovelli, F.; Martinelli, G.L.; Muir, D.F.; ... ; Tamburino, C. 2019
Aims: Treatment pathway optimisation in TAVI should include timely patient discharge with a minimised risk for out-of-hospital adverse events. The aim of this study was to define a standardised set... Show moreAims: Treatment pathway optimisation in TAVI should include timely patient discharge with a minimised risk for out-of-hospital adverse events. The aim of this study was to define a standardised set of risk criteria that allows a safe and timely discharge, to validate their appropriateness prospectively in different centres and multiple European countries, and to assess post-discharge outcomes.Methods and results: We defined and validated the adequacy of a set of discharge criteria and its ability to predict timely and safe discharge properly after the intervention in a prospective, European, multi centre registry. A total of 502 unselected patients were enrolled at 10 sites in three countries. The primary endpoint, defined as a composite of all-cause mortality, vascular access-related complications, permanent pacemaker implantation, stroke, re-hospitalisation due to cardiac reasons, kidney failure and major bleeding at 30 days, was reached in 12.9% of patients (95% CI: 11.3-16.5). The overall 30-day mortality was 1.1% (95% CI: 0.2-2.0), and the rates of stroke/TIA 1.7% (95% CI: -0.6 to 4.0), PPI 7.3% (95% CI: 5.8-8.9), major vascular complications 1.9% (95% CI: 0.7-3.1), major/life-threatening bleeding 2.4% (95% CI: 1.0-3.8) and cardiac re-hospitalisation 3.7% (95% CI: 1.4-6.0). Patients appropriately discharged early had a significantly lower risk of the primary endpoint (7.0 vs. 26.4%; p<0.001) which was reflected in some of its relevant components: stroke (0.0 vs. 2.8%; p=0.015), PPI (4.3 vs. 15.9%; p<0.001), major vascular complications (0.3 vs. 4.7%; p=0.004) and major/life-threatening bleeding (0.3 vs. 6.5%; p<0.001).Conclusions: We validated the appropriateness of a pre-specified set of risk criteria that allows a safe and timely discharge. The lute of 30-day complications did not reveal any risk increase with this strategy compared with the reported outcomes in major TAVI trials and registries. Show less
Barbanti, M.; Baan, J.; Spence, M.S.; Iacovelli, F.; Martinelli, G.L.; Saia, F.; ... ; Tamburino, C. 2017
Upon demixing, an aqueous solution of a polyelectrolyte and an incompatible neutral polymer yields two phases separated by an interface with an ultralow tension. Here, both in theory and experiment... Show moreUpon demixing, an aqueous solution of a polyelectrolyte and an incompatible neutral polymer yields two phases separated by an interface with an ultralow tension. Here, both in theory and experiment, we study this interfacial tension in detail: how it scales with the concentrations of the polymers in the two phases and how it is affected by the interfacial difference in the electrical potential. Experiments are performed on an aqueous model system of uncharged dextran and charged nongelling gelatin. The experimental tension scales to the power ∼3 with the tie-line length in the phase diagram of demixing, in agreement with mean-field theory where space is filled with a binary mixture of polymer blobs. The interfacial electrical potential difference is experimentally found to decrease the interfacial tension in a way that is consistent with Poisson–Boltzmann theory inspired from Frenkel and Verwey–Overbeek. Show less
Electric charge at the water-water interface of demixed solutions of neutral polymer and polyelectrolyte decreases the already ultralow interfacial tension. This is demonstrated in experiments on... Show moreElectric charge at the water-water interface of demixed solutions of neutral polymer and polyelectrolyte decreases the already ultralow interfacial tension. This is demonstrated in experiments on aqueous mixtures of dextran (neutral) and nongelling fish gelatin (charged). Upon phase separation, electric charge and a potential difference develop spontaneously at the interface, decreasing the interfacial tension purely electrostatically in a way that can be accounted for quantitatively by Poisson-Boltzmann theory. Interfacial tension is a key property when it comes to manipulating the water-water interface, for instance to create novel water-in-water emulsions. Show less
Tromp, H.R.; Vis, M.; Erné, B.H.; Blokhuis, E.M. 2014
The properties of interfaces are discussed between coexisting phases in phase separated aqueous solutions of polymers. Such interfaces are found in food, where protein-rich and polysaccharide-rich... Show moreThe properties of interfaces are discussed between coexisting phases in phase separated aqueous solutions of polymers. Such interfaces are found in food, where protein-rich and polysaccharide-rich phases coexist. Three aspects of such interfaces are highlighted: the interfacial profiles in terms of polymer composition and polymer concentration, the curvature dependence of the interfacial tension, and the interfacial potential, arising when one of the separated polymers is charged. In all three cases a theoretical approach and methods for experimental verification are presented. Show less
