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Background Conventional radiographs of hands and feet are used to depict structural damage in rheumatoid arthritis (RA). This is also commonly done in clinical practice in symptomatic patients at risk for RA (clinically suspect arthralgia (CSA)), but its rationale is unclear. We aimed to investigate the prevalence of radiographic erosive disease in patients with CSA and its progression over time.Methods Patients with symptomatic arthralgia of the Leiden CSA cohort were studied during 2-year follow-up or until development of inflammatory arthritis (IA). Erosive disease was defined according to the radiologist, or according to the RA-specific erosive definition in light of the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2010 RA criteria. Serial radiographs were evaluated according to the Sharp van der Heijde Scoring method (SHS) and radiographic erosive progression was determined. Additionally, it was evaluated if baseline erosive disease associated with IA development. Analyses were stratified for anticitrullinated protein antibody status.Results 1497 radiographs of hands and feet of 749 patients with CSA were studied. Median SHS-erosion score at baseline was 0 (IQR 0–1). RA-specific erosive disease was present in 1.7% according to the radiologist, and 2.5% according to the ACR/EULAR criteria. No patients with CSA progressed ≥5 SHS-erosion points during follow-up. Erosive disease at CSA onset was not associated with IA development (HR 0.98 (95% CI 0.40 to 2.44)).Conclusions At CSA onset, radiographic erosive disease is rare. In addition, it is rarely progressive within the CSA phase and not predictive for IA development. Therefore, for clinical practice, routinely made radiographs of hands and feet (such as regularly done at RA diagnosis) can be omitted in the at-risk stage of arthralgia.

Objectives Secondary prevention of rheumatoid arthritis (RA) is generally considered potentially impactful because the entire RA population is believed to experience a symptomatic ‘pre-RA’ phase. We wondered whether this dogma is correct. Therefore we investigated an inception cohort of patients with newly diagnosed RA and studied among them patients who did and did not present with preceding arthralgia at risk for RA.Methods Consecutively diagnosed patients with RA between 2012 and 2022 were studied (n=699). These patients had either directly presented with clinically apparent arthritis, or had first presented with clinically suspect arthralgia (CSA). Clinical characteristics at symptom onset and RA diagnosis were compared. Whether certain characteristics frequently occurred together was studied using a K-means algorithm after dimension reduction with partial least squares discriminant analysis. To validate that groups differed in long-term outcomes, sustained disease-modifying anti-rheumatic drug-free remission (SDFR) of the groups was studied during a median follow-up of 5.3 years.Results Patients with RA who had first presented with CSA were younger, more often had a gradual symptom onset and were more often anti-citrullinated protein antibodies (ACPA)-positive. Studying characteristics at symptom onset and RA diagnosis revealed four patient clusters, of which two clusters included almost all patients with a preceding CSA phase. Patients in these two clusters (55% of RA population) were younger, had a gradual symptom onset, longer symptom duration and were more frequently ACPA-positive. Patients with RA in these clusters achieved SDFR less often (HR 0.51 (95% CI 0.37 to 0.68)) than the patients with RA in the two clusters where preceding CSA was infrequent/absent.Conclusion These data suggest the notion that the entire RA population has an identifiable symptomatic risk stage should be refuted. This may impact on the scope of preventive interventions targeting the symptomatic risk phase.

Background: We aimed to gain more insight into autonomy of older people with intellectual disabilities in a residential care facility in making choices. Methods: We performed a descriptive ethnographic study in a residential facility in the Netherlands for 22 persons, aged 54-89 years, with mild to moderate intellectual disabilities (IQ <70) and low social-emotional development levels. We combined participant observations and qualitative interviews. Results: Based on the observations, the main themes for the interviews were established. Residents indicated to be free to make independent choices, and experienced less autonomy with regard to health issues and finances. Support staff stated that residents' level of autonomy depends on residents' characteristics, needs, preferences, the attitude of support staff and the rules of the care institution. Conclusion: Residents had a clear view on their autonomy in making independent choices. Support staff is mindful of preserving residents' autonomy, which in practice is limited.

Objectives Although joint swelling is traditionally interpreted as synovitis, recent imaging studies showed that there is also inflammation of tenosynovium and intermetatarsal bursae in the forefoot. We aimed to increase our understanding of differences and similarities regarding forefoot involvement between ACPA-positive and ACPA-negative rheumatoid arthritis (RA) at diagnosis. Therefore, we (1) compared metatarsophalangeal (MTP) joint counts, walking disabilities and inflamed tissues between ACPA groups and (2) studied associations of joint swelling/tenderness and walking disabilities with underlying inflamed tissues within ACPA groups.Methods 171 ACPA-positive and 203 ACPA-negative consecutively diagnosed patients with RA had a physical joint examination (swollen joint count-66/tender joint count-68), filled a Health Assessment Questionnaire including the domain walking and underwent MRI of the MTP joints at diagnosis. Synovitis, tenosynovitis, osteitis and intermetatarsal bursitis (IMB) were assessed. Findings in age-matched healthy controls were applied to define abnormalities on MRI.Results While ACPA-negative RA patients had more swollen joints (mean SJC 8 vs 6 in ACPA-positives, p=0.003), the number of swollen MTP joints was similar (mean 1 in both groups); walking disabilities were also equally common (49% vs 53%). In contrast, inflamed tissues were all more prevalent in ACPA-positive compared with ACPA-negative RA. Within ACPA-positive RA, IMB was associated independently with MTP-joint swelling (OR 2.6, 95% CI 1.4 to 5.0) and tenderness (OR 3.0, 95% CI 1.8 to 5.0). While in ACPA-negatives, synovitis was associated independently with MTP-joint swelling (OR 2.8, 95% CI 1.4 to 5.8) and tenderness (OR 2.5, 95% CI 1.3 to 4.8). Tenosynovitis contributed most to walking disabilities.Conclusions Although the forefoot of ACPA-positives and ACPA-negatives share clinical similarities at diagnosis, there are differences in underlying inflamed tissues. This reinforces that ACPA-positive and ACPA-negative RA are different entities.

Objectives Obesity is a known risk factor for developing rheumatoid arthritis (RA). However, it is unclear whether obesity exerts its risk effect during the asymptomatic or the symptomatic clinically suspect arthralgia (CSA) phase of risk. To improve understanding of the effect of obesity on RA development, we aimed to (1) compare body mass index (BMI) at CSA onset to BMI of the general population and (2) study within CSA patients if obesity increases the risk for progression to RA.Methods 1107 symptomatic persons at risk for RA from four cohorts (CSA Leiden, CSA Rotterdam, SONAR and TREAT EARLIER placebo arm) were studied. For the first aim, baseline BMI was compared with age-matched/sex-matched BMI of the general population. Patients were stratified for anticitrullinated protein antibody (ACPA) status. Regarding the second aim, the association between BMI and inflammatory arthritis (IA) development during 2 years was studied with Cox regression analysis within each cohort and via meta-analysis in all cohorts.Results CSA patients of all cohorts were more often obese than the general population (respectively 21.9% vs 14.0%, 25.7% vs 14.5%, 26.7% vs 14.5% and 33.3% vs 14.9%, in CSA Leiden, CSA Rotterdam, SONAR, TREAT EARLIER placebo arm). Both ACPA-positive and ACPA-negative CSA patients had a higher frequency of obesity. Within CSA, obesity was not associated with IA development compared to normal weight (pooled effect in meta-analysis of four cohorts HR 1.01 (95% CI 0.93 to 1.08)).Conclusions Obesity is not associated with RA development within CSA patients but BMI has already increased in CSA compared to the general population. Obesity, therefore, presumably exerts its risk effect at an early asymptomatic phase of RA development, rather than being associated with the disease processes that ultimately result in clinical arthritis.

Compression clothes are marketed to relieve anxiety and decrease hyperactivity in children with autism. However, few studies have examined the impact of compression for individuals with autism spectrum disorder (ASD). In this study, nine children with autism were observed during Applied Behavioral Analysis therapy sessions while wearing compression clothing. The participants were randomly assigned to wear compression clothing for either their first five sessions or their last five sessions. Videos of the therapy sessions were reviewed and each child’s “off task” behavior was identified in the following domains: motor, verbal, and visual. In addition, frequency of the child’s repetitive behaviors and external visual stimuli were recorded. The compression clothes failed to increase task participation or reduce the participants’ repetitive behavior suggesting that the clothing may not contribute to professional practice of ABA therapy.

Background: Little is known about how to involve people with intellectual disabilities in making decisions about treatment and care in their palliative phase. We aimed to reach a consensus about a shared decision-making (SDM) conversation aid for people with intellectual disabilities, relatives, and healthcare professionals. Methods: In a Delphi process, an expert panel of 11 people with intellectual disabilities, 14 relatives, and 65 healthcare professionals completed online questionnaires about the relevance and feasibility of a draft conversation aid. Results: In Round 1, components were rated as (very) relevant by 70-98% of participants (M = 87%). In Round 2, after amending the aid in response to feedback, relevance ratings were 67-97% (M = 90%) and feasibility ratings 66-86% (M = 77%). The final version consists of four themes: who are you; illness/end-of-life; making decisions; and evaluating the decision. Conclusion: The consensus-based conversation aid is considered sufficiently relevant and feasible to be implemented in practice.

The present study aimed to explore the situation of people with intellectual disabilities and their families during the first three months of the Russian invasion in Ukraine. Utilising a snowball sampling procedure, five participants were recruited to participate in this descriptive qualitative study. Thematic analysis was used to analyse the interviews. Five overarching themes emerged from the data: 1) The physical and mental well-being of people with intellectual disabilities was threatened due to a lack of fulfilment of basic needs; 2) People with intellectual disabilities experienced difficulties in finding safety within air-raid shelters; 3) People with intellectual disabilities and their families could only flee the country with help and support; 4) Creative solutions were developed to help keep in touch with and support people with intellectual disabilities and their families; and 5) Fear regarding the quality of life of and support for people with intellectual disabilities in the near future. Point of interest: This research is important as it raises attention for the vulnerable position of people with intellectual disabilities and their families in Ukraine during the war. People with intellectual disabilities experience difficulties when trying to access the safety of air-raid shelters. This study showed how people with intellectual disabilities and their families depend on help and support to be able to flee the country. During the war, people find creative ways to support people with intellectual disabilities and their families. People fear for the future quality of life and support for people with intellectual disabilities in Ukraine after the war. [ABSTRACT FROM AUTHOR]

Abstract Introduction Arthralgia and MRI-detected subclinical inflammation can precede the development of clinically evident rheumatoid arthritis (RA). However, part of the patients presenting with clinically suspect arthralgia (CSA) do not progress to RA. In these ‘non-progressors’, we aimed to study the frequencies of spontaneous improvement of arthralgia and its relation with the course of subclinical inflammation. Methods Between April 2012 and April 2015, 241 patients were considered at risk for RA based on the clinical presentation and included in the CSA cohort. One hundred fifty-two patients with complete data on clinical follow-up did not develop clinical arthritis, of which 98 underwent serial 1.5T MRI scans (wrist, MCP2–5, and MTP1–5 joints) at baseline and after 2 years. MRI scans were scored for synovitis, tenosynovitis, and bone marrow oedema (summed: MRI inflammation score). MRI scores were compared to scores of symptom-free persons. Results After a 2-year follow-up, 33% of the ‘non-progressors’ had complete resolution of symptoms; 67% had no symptom resolution and were diagnosed as persistent CSA (44%), osteoarthritis (10%), and tendinomuscular complaints (13%). With symptom-free controls as a reference, patients without resolution did not have increased MRI scores at any time point. However, patients achieving resolution of symptoms had increased MRI inflammation scores at baseline (4.0 vs. 2.6, p = 0.037), but not after 2 years (3.0 vs. 2.6; p = 0.57), and during follow-up, their MRI inflammation score decreased significantly (p = 0.036). Conclusions A subgroup of CSA patients that did not progress to RA had spontaneous improvement of symptoms and resolution of subclinical joint inflammation. This time relationship suggests that symptoms and inflammation were causally related in these patients. Further research is needed to identify the mechanisms underlying the resolution of inflammation.

Objectives Healthcare professionals other than rheumatologists experience difficulties in detecting early inflammatory arthritis (IA) by joint examination. Self-reported symptoms are increasingly considered as helpful and could be incorporated in online tools to assist healthcare professionals, but first their discriminative ability must be assessed. As part of this effort, we evaluated whether inquiring about functional impairments could aid early IA identification.Design Cross-sectional derivation and validation study.Setting Data from two Early Arthritis Recognition Clinics (EARC) in the Netherlands were studied, which are easy access outpatient rheumatology clinics intermediary between primary and secondary care for patients in whom general practitioners suspect but are unsure about IA presence.Participants Between 2010 and 2014, 997 patients consecutively visited the Leiden-EARC (derivation cohort). Patients consecutively visiting the Groningen EARC (2010–2014, n=506) and Leiden-EARC (2015–2018, n=557) served as validation cohorts.Primary and secondary outcome measures Physical functioning was assessed with the Health Assessment Questionnaire Disability-Index (HAQ); IA presence by physical joint examination by rheumatologists. HAQ questions were studied individually regarding discriminative ability for IA presence. For the best discriminating question, ORs and positive predictive values (PPVs) for IA presence were determined.Results IA was ascertained in 43% (derivation cohort), 53% and 35% (validation cohorts). In the derivation cohort, IA presence associated with higher mean HAQ scores (0.84 vs 0.73, p=0.003). One question on difficulties with dressing equalled discriminative ability of the total HAQ score. ‘Difficulties with dressing’ yielded ORs for IA presence of 1.8 (95% CI 1.4 to 2.4) in the derivation cohort; 2.0 (1.4 to 2.9) and 2.1 (1.5 to 3.1) in the validation cohorts. After adjustments for clinical characteristics these were 1.7 (1.3 to 2.3), 1.6 (1.1 to 2.5) and 1.9 (1.2 to 2.9). PPVs (probabilities of IA for positive answers) ranged 42%–60% and negative predictive values (probabilities of no IA for negative answers) ranged 57%–74%.Conclusions Patient-reported difficulties with dressing in patients with suspected IA associated with actual IA presence. Although further validation is required, for example, in primary care, this simple question could be of help in future early IA detection tools for healthcare professionals with limited experience in joint examination.

Abstract Background The presence of autoantibodies is considered an important characteristic of rheumatoid arthritis (RA); therefore, both anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are included in the 2010 classification criteria for rheumatoid arthritis (RA). However, a considerable number of RA patients lack both these autoantibodies. Recently, several novel autoantibodies have been identified but their value for the classification of RA patients is unclear. Therefore, we studied the value of novel autoantibodies using the presence of anticarbamylated protein (anti-CarP) antibodies as an example for predicting RA development in patients with undifferentiated arthritis (UA). Methods There were 1352 UA patients included in the Leiden Early Arthritis Clinic (EAC) cohort according to the 1987 criteria. When the 2010 criteria were used, there were 838 UA patients. Of these, we evaluated whether they fulfilled the 1987 or 2010 criteria after 1 year, respectively. Logistic regression analyses were performed with RA as outcome and ACPA, RF, and anti-CarP antibodies as predictors. Analyses were repeated after stratification for ACPA and RF. Results Thirty-three percent of the 1987-UA patients and 6% of the 2010-UA patients progressed to RA during the first year of follow-up. For the 1987-UA patients, anti-CarP antibodies were associated with progression to RA, an association which remained when a correction was made for the presence of ACPA and RF (odds ratio (OR) 1.7, 95% confidence interval (CI) 1.2–2.4). After stratification for ACPA and RF, anti-CarP antibodies were associated with progression to RA only for ACPA- and RF-negative patients (OR 2.1, 95% CI 1.3–3.7). For the 2010-UA patients, anti-CarP antibodies were associated with progression to RA; however, they were not when a correction was made for the presence of ACPA and RF (OR 0.8, 95% CI 0.3–2.1). Conclusions Our finding that anti-CarP antibodies have no additional value when RA is defined according to the 2010 criteria might be inherent to the composition of the 2010 criteria and therefore might also apply to other novel autoantibodies. Potentially it would be interesting to evaluate other, non-autoantibody biomarkers.

Objective Obesity conveys a risk for RA development, while paradoxically, associating with less radiographic progression after RA diagnosis. Using MRI we can study this surprising association in detail from MRI-detected synovitis and osteitis to MRI-detected erosive progression, which precedes radiographic progression. Previous research suggested obesity associates with less osteitis and synovitis. We therefore aimed to (i) validate the previously suggested association between BMI and MRI-detected osteitis/synovitis; (ii) study whether this is specific for ACPA-positive or ACPA-negative RA or also present in other arthritides; (iii) study whether MRI-detected osteitis associates with MRI-detected erosive progression; and (iv) study whether obesity associates with MRI-detected erosive progression. Methods We studied 1029 early arthritis patients (454 RA, 575 other arthritides), consecutively included in Leiden Early Arthritis Clinic. At baseline patients underwent hand-and-foot MRI that were RAMRIS-scored, and 149 RA patients underwent follow-up MRIs. We studied associations between baseline BMI and MRI-detected osteitis/synovitis (using linear regression), and erosive progression (using Poisson mixed models). Results In RA, higher BMI associated with less osteitis at disease onset (β = 0.94; 95% CI: 0.93, 0.96) but not with synovitis. Higher BMI associated with less osteitis in ACPA-positive RA (β = 0.95; 95% CI: 0.93, 0.97), ACPA-negative RA (β = 0.97; 95% CI: 0.95, 0.99) and other arthritides (β = 0.98; 95% CI: 0.96, 0.99). Over 2 years, overweight and obesity associated with less MRI-detected erosive progression (P  = 0.02 and 0.03, respectively). Osteitis also associated with erosive progression over 2 years (P  < 0.001). Conclusions High BMI relates to less osteitis at disease onset, which is not confined to RA. Within RA, high BMI and less osteitis associated with less MRI-detected erosive progression. This suggests that the protective effect of obesity on radiographic progression is exerted via a path of less osteitis and subsequently fewer MRI-detected erosions. [ABSTRACT FROM AUTHOR]

The concept of a 'window of opportunity' in treating a disease assumes the existence of a time frame during which the trajectory of the disease can be effectively and permanently modified. In rheumatoid arthritis (RA), optimal timing of this period is presumed to be during the phase before arthritis is clinically apparent and disease is diagnosed. Several proof-of-concept trials of treatment during the 'arthralgia' phase of RA have been completed in the past 4 years, with the underlying notion that temporary treatment at this stage could prevent the development of RA or induce a sustained reduction in the burden of disease. This Review summarizes the results of these trials and reflects on the outcomes in relation to the patients' perspectives. Overall, the majority of symptomatic at-risk individuals could benefit from a fixed period treatment, even if RA does not develop. Various factors must be taken into consideration when translating these findings into clinical practice. More evidence is needed to target the individuals at highest risk, and additional tools are needed to monitor treatment and guide decisions about whether treatment can be discontinued. Without these tools, there is a paradoxical risk of seemingly increasing the incidence of the disease and prolonging disease duration, which is the opposite of what the concept of intervening in the window of opportunity entails. Treatment of patients with arthralgia during the 'window of opportunity' could prevent disease development or a severe disease course. This Review summarizes available information on the completed and ongoing prevention trials in rheumatoid arthritis, including patient preferences and future considerations. Key points: The therapeutic 'window of opportunity' in rheumatoid arthritis presumes that disease processes are less matured and more modifiable in the symptomatic pre-arthritis phase, fuelling the design of 'prevention trials'. Although the populations studied in these trials varied slightly, the at-risk individuals included those with a combination of symptoms (clinically suspect arthralgia), autoantibodies and subclinical inflammation on imaging. The first 'proof-of-concept' prevention trials suggest that disease modification could be possible with temporary treatment initiated in an at-risk pre-arthritis phase. Nonetheless, treatment in a symptomatic at-risk phase without clinical arthritis is not yet recommended by any treatment guideline. Before findings can be implemented, validated tools are needed for risk stratification to guide treatment-start decisions and for monitoring (a 'disease activity score for clinically suspect arthralgia') to guide treatment-withdrawal decisions. [ABSTRACT FROM AUTHOR]

Objective: The natural trajectory of clinical arthritis progression at the tissue level remains elusive. We hypothesized that subclinical inflammation in different joint tissues (synovitis, tenosynovitis, osteitis) increases in a distinct temporal order in patients with clinically suspect arthralgia (CSA) who develop rheumatoid arthritis (RA) and subsides in a different sequence when CSA spontaneously resolves. Methods: We studied 185 serial magnetic resonance images (MRIs) from CSA patients with subclinical joint inflammation from the placebo arm of the TREAT EARLIER trial: 52 MRIs from 21 RA progressors (MRIs conducted at 1 year before, at 4 months before, and upon RA development), and 133 MRIs from 35 patients with spontaneous resolution of pain (MRIs conducted at baseline and at 4, 12, and 24 months). MRIs were scored for osteitis, synovitis, and tenosynovitis. We used cross‐lagged models to evaluate 2 types of time patterns between pairs of inflamed tissues: a simultaneous pattern (coinciding changes) and a subsequent pattern (inflammatory changes in 1 tissue preceding changes in another tissue). Results: In patients who developed RA, synovitis, tenosynovitis, and osteitis increased simultaneously. Increasing osteitis occurred in the final 4 months before RA diagnosis, following incremental tenosynovitis and synovitis changes during the 1 year to 4 months before diagnosis (P < 0.01). In anti–citrullinated protein antibody (ACPA)‐positive and ACPA‐negative patients who progressed to RA, osteitis increased just before RA development. In patients with pain resolution, simultaneous decreases in synovitis, tenosynovitis, and osteitis occurred, with tenosynovitis decreasing in the first 4 months after CSA onset preceding decreasing synovitis and osteitis during 4–12 months (P = 0.02 and P < 0.01). Conclusion: We identified natural sequences of subclinical inflammation in different joint tissues, which deepens our understanding of clinical arthritis and RA development. During RA progression, increasing osteitis followed previous increases in tenosynovitis and synovitis. During pain resolution, tenosynovitis decreased first, followed by decreasing synovitis and osteitis. [ABSTRACT FROM AUTHOR]

Spastic syndrome is a chronic, progressive disorder of adult cattle characterized by episodes of sudden involuntary muscle contractions or spasms of the extensor and abductor muscles of one or both hind limbs. In this study, a case-control genome-wide association study (GWAS) was performed on an adult Holstein cattle cohort. Based on the 50 K and high-density (HD) SNP panel GWAS, we identified 98 and 522 SNPs, respectively. The most significant genomic regions identified are located on BTA9 at approximately 87 megabase pairs (Mb) and BTA7 between 1 and 20 Mb. Functional analyses of significant SNPs identified genes associated with muscle contraction, neuron growth or regulation, and calcium or sodium ion movement. Two candidate genes (FIG4 and FYN) were identified. FIG4 is ubiquitously expressed in skeletal muscle and FYN is involved with processes such as forebrain development, neurogenesis, locomotion, neurogenesis, synapse development, neuron migration, and the positive regulation of neuron projection development. The CACNA1A gene, which codes for a calcium channel subunit protein in the calcium signaling pathway, seems the most compelling candidate gene, as many calcium ion channel disorders are non-degenerative, and produce spastic phenotypes. These results suggest that spastic syndrome is of polygenic inheritance, with important genomic areas of interest on BTA7 and BTA9. [ABSTRACT FROM AUTHOR]