Lessons learned from a pilot implementation of physical activity recommendations in axial spondyloarthritis exercise group therapy

Background The Ankylosing Spondylitis Association of Switzerland (SVMB) aimed to implement physical activity recommendations (PAR) within their exercise groups (EGs). The PAR promote exercise in all fitness dimensions at the correct dose. To implement the PAR within EGs, they were translated into a new EG concept with five key activities: (a) training for supervising physiotherapists (PTs), (b) correctly dosed exercises in all fitness dimensions, (c) exercise counselling, (d) bi-annual fitness assessments, and (e) individual exercise training, in addition to EG. All these activities were realized in close coordination with SVMB management. Objectives To analyse the implementation success by evaluating adherence/fidelity, feasibility, and satisfaction at the patient, PTs, and organisational level. Methods The five key activities of the new EG concept were developed, executed, and assessed after 6 months. The primary outcomes for implementation success were adherence of patients to the recommended exercise behaviour, self-reported by electronic diary; fidelity of PTs to the new concept, self-reported by diary; SVMB organisational changes. Secondary outcomes were feasibility and satisfaction with the new EG concept at all three levels. The tertiary outcome, to evaluate the effectiveness of PAR, was patient fitness, assessed through fitness assessments. Results 30 patients with axSpA (ten women, mean age 58 ± 9 years) and four PTs (three women, mean age 46 ± 9 years) participated. The patients' self-reporting of adherence to the PAR was insufficient (43%), possibly due to technical problems with the electronic dairy. The PTs' fidelity to the new EG concept was satisfactory. On all levels, the new concept was generally perceived as feasible and useful for supporting personalised exercise.The frequency of exercise counselling and the fitness assessments was found by patients and PTs to be too high and rigid. Patients' cardiorespiratory fitness [ES 1.21 (95%CI 0.59, 1.89)] and core strength [ES 0.61 (95%CI 0.18, 1.06)] improved over the 6 months. Conclusions The pilot implementation of PAR showed acceptance and satisfaction to be sufficient, thus confirming the need for evidence-based EGs, provided by a patient organisation in order to support active PA behaviour. However, adaptations are necessary to increase its feasibility for nationwide implementation. Trial Registration: SNCTP, SNCTP000002880. Registered 31 May 2018, https://www.kofam.ch/en/snctp-portal/search/0/study/42491.

Association of rheumatoid arthritis and its severity with human leukocytic antigen-DRB1 alleles in Kurdish region in North of Iraq

Background Rheumatoid arthritis is a complex multifactorial chronic disease, the importance of human leukocytic antigen (HLA) as a major genetic risk factor for rheumatoid arthritis was studied worldwide. The objective of this study is to identify the association of HLA-DRB1 subtypes with rheumatoid arthritis and its severity in Kurdish region. Methods A case–control study recruited 65 rheumatoid arthritis patients and 100 healthy individuals as control group all over the Kurdistan region/Iraq. Both patient and control groups are genotyped using polymerase chain reaction with sequence specific primer. Anti-CCP antibodies were measured by ELISA test. Rheumatoid factor, C-reactive protein, and disease activity score 28 which measured by DAS-28 values were calculated. The DAS-28 was used to assess the clinical severity of the patients. Results HLA-DRB1-0404 and HLA-DRB1-0405 frequencies showed a strong association with disease susceptibility (P < 0.001). The frequency of HLA-DRB1-0411 and HLA-DRB1-0413 were significantly higher in control group (P < 0.001). The frequency of rheumatoid factor and Anti-CCP were significantly higher among shared epitope-positive patients compared to shared epitope-negative patients (P < 0.001). Regarding the disease activity by DAS-28, rheumatoid arthritis patients didn’t show significant difference between the shared epitope-positive and shared epitope-negative patients. Conclusions HLA-DR0404 and HLA-DR0405 alleles are related to RA, while HLA-DR1-0411 and HLA-DRB1-0413 protect against RA in the Kurdistan region in the North of Iraq.

Fatigue is associated with disease activity in some, but not all, patients living with rheumatoid arthritis: disentangling “between-person” and “within-person” associations

Background Previous research has shown an unclear and inconsistent association between fatigue and disease activity in patients with rheumatoid arthritis (RA). The aim of this study was to explore differences in “between-person” and “within-person” associations between disease activity parameters and fatigue severity in patients with established RA. Methods Baseline and 3-monthly follow-up data up to one-year were used from 531 patients with established RA randomized to stopping (versus continuing) tumor necrosis factor inhibitor treatment enrolled in a large pragmatic trial. Between- and within-patient associations between different indicators of disease activity (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], swollen and tender joint count [ SJC and TJC], visual analog scale general health [VAS-GH]) and patient-reported fatigue severity (Bristol RA Fatigue Numerical Rating Scale) were disaggregated and estimated using person-mean centering in combination with repeated measures linear mixed modelling. Results Overall, different indices of disease activity were weakly to moderately associated with fatigue severity over time (β’s from 0.121 for SJC to 0.352 for VAS-GH, all p’s < 0.0001). Objective markers of inflammation (CRP, ESR and SJC) were associated weakly with fatigue within patients over time (β’s: 0.104–0.142, p’s < 0.0001), but not between patients. The subjective TJC and VAS-GH were significantly associated with fatigue both within and between patients, but with substantially stronger associations at the between-patient level (β’s: 0.217–0.515, p’s < 0.0001). Within-person associations varied widely for individual patients for all components of disease activity. Conclusion Associations between fatigue and disease activity vary largely for different patients and the pattern of between-person versus within-person associations appears different for objective versus subjective components of disease activity. The current findings explain the inconsistent results of previous research, illustrates the relevance of statistically distinguishing between different types of association in research on the relation between disease activity and fatigue and additionally suggest a need for a more personalized approach to fatigue in RA patients. Trial registration Netherlands trial register, Number NTR3112.

Genetic assessment of hyperuricemia and gout in Asian, Native Hawaiian, and Pacific Islander subgroups of pregnant women: biospecimens repository cross-sectional study

Background Gout, an inflammatory condition, is characterized by the precipitation of monosodium urate crystals (MSU) in or around distal joints. The latter is caused by chronic hyperuricemia (HU)—high urate levels in the blood. Genetic variations in urate transporters play a significant role in determining urate levels within the human body, rendering some racial and ethnic groups more or less susceptible to developing either HU or gout. This study aims to estimate the frequencies of HU and gout risk alleles in Asian, Native Hawaiian, and Pacific Islander subgroups, using biorepository DNA samples. Methods The biospecimens repository at the University of Hawai’i provided DNA samples of consented post-partum women of Japanese, Filipino, Korean, Native Hawaiian, Samoan, and Marshallese descent. The DNA was previously extracted from maternal blood and genotyped at the Genomics and Bioinformatics Shared Resource, Cancer Center (Honolulu, HI). Nine urate genes: ABCG2, SLC2A9, SLC16A9, GCKR, SLC22A11, SLC22A12, LRR16A, PDZK1, and SLC17A1, were selected due to their significant association with HU and gout risk. Hardy–Weinberg Equilibrium (HWE) for genotype frequencies was assessed, using the Chi-Square test with p < 0.006 for statistical significance. Allele frequencies in our study were then compared to EUR from the 1000 Genomes Project Database Phase III, using Chi-square or Fisher's exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with p < 0.006 for statistical significance. Results Our study involved 1059 post-partum women 18-year-old or older who self-reported their respective race and ethnicity, including Asian, Native Hawaiian, and Pacific Islander ancestry. The Asian subgroups included Japanese, Filipino, and Korean. The Pacific Islander subgroups included Marshallese and Samoan. None of the study participants had a history of gout. We excluded the PDZK1 gene from the final analysis due to its deviation from HWE (p < 0.006) across all the population subgroups, with eight loci remaining for cross-subgroup comparisons. Compared to EUR, the genetic polymorphism frequencies were significantly different-8/8 in Japanese, 6/8 in Korean, 6/8 in Filipino, 8/8 in Samoan, 6/8 in Native Hawaiian, and 6/8 in Marshallese. HU and gout risk alleles indices were 8, 6, 5, 5, 4, and 4 in Japanese, Filipino, Korean, Samoan, Marshallese, and Native Hawaiian, respectively. The percentage of cumulative risk alleles was 100% in both Japanese and Filipino, followed by 83.5% in Korean. Conclusions Compared to EUR, Asian subgroups, particularly Japanese, Filipino, and Korean, had the highest percentage of the cumulative uric acid risk alleles. These results could partly explain the increased risk of developing gout among some Asian ancestral subgroups compared to EUR.

Impact of demographic, clinical, and treatment compliance characteristics on quality of life of Venezuelan patients with systemic lupus erythematosus

Background We have here assessed the impact of demographic, clinical, and treatment compliance characteristics on health-related quality of life (HRQoL) of Venezuelan patients with systemic lupus erythematosus (SLE). We have used a disease-specific questionnaire, the Lupus Quality of Life (LupusQoL), validated in our patient population, to measure HRQoL. Methods A cross-sectional study was conducted among 100 patients with SLE from outpatient clinics. Patients completed a form with demographic, clinical, and treatment compliance data, and the LupusQoL questionnaire. HRQoL was classified as better or worse according to previously established cut-off points for this patient population. Spearman’s r test was used to determine the correlations between age, years of education, disease duration, SLEDAI, and SLICC-DI with the eight domains of the LupusQoL. Mann–Whitney U test was used to compare the HRQoL between the two groups of patients according to treatment compliance. Binomial logistic regression using the backward stepwise selection method was performed to identify the risk factors associated with each of the eight domains of the LupusQoL among patients with inactive (SLEDAI < 4) and active (SLEDAI ≥ 4) SLE. Results HRQoL of our patients was classified as better in all domains of the LupusQoL. Age correlated negatively with all domains of the LupusQoL, except with “burden to others”, and disease activity correlated negatively with all domains of the LupusQoL, except with “intimate relationships” and “burden to others” (p < 0.05). Patients who fully complied with indicated treatment had higher scores in “physical health” domain compared to patients who did not comply with at least one of the prescribed medications (p < 0.05). In patients with active SLE, a risk factor associated with worse “planning” and “intimate relationships” was advanced age, while having had SLE flare-ups in the previous six months was a risk factor associated with worse “physical health” (p < 0.05). Conclusion Age and disease activity were negatively correlated with almost all domains of the LupusQoL, and treatment compliance was associated with higher score in the “physical health” domain. Disease control and treatment compliance should be the main goals for a better HRQoL in our patients with SLE.

Macrophage activation syndrome in MDA5 antibody-positive dermatomyositis and COVID-19 infection

Background Macrophage activation syndrome (MAS) is a rare multiorgan system disorder that may present as a fatal complication of underlying rheumatological disease, including dermatomyositis. Case presentation Here, we report the case of a 65-year-old Caucasian female with a history of psoriasis and a recent diagnosis of Coronavirus disease 2019 (COVID-19) who presented with progressive generalized weakness, joint pains, an erythematous rash, shortness of breath, and weight loss. She was ultimately diagnosed with biopsy-confirmed melanoma differentiation-associated protein 5 (MDA5)-positive dermatomyositis complicated by MAS, requiring intravenous immunoglobulin and high-dose methylprednisolone. Conclusions This report serves as a clinical reminder of the rare, yet clinically relevant association between MDA5-positive dermatomyositis and MAS, as well as highlights the potential contribution of other immune system activating diseases, such as COVID-19, associated with a cytokine storm and hyperinflammatory state.

The effectiveness of e-learning in patient education delivered to patients with rheumatoid arthritis: The WebRA study—protocol for a pragmatic randomised controlled trial

Background Patient education is integral to the treatment and care of patients with rheumatoid arthritis. Change is taking place in the organisation of healthcare systems because of a demographic shift towards ageing populations, an increasing use of technology and advancements in digital technologies, allowing for new interventions. This study will aim to evaluate the effectiveness of a newly developed e-learning patient education programme based on self-management that targets patients with rheumatoid arthritis. Methods A pragmatic multi-centre randomised controlled trial is planned. We intend to recruit approximately 200 patients with a new diagnosis (< 3 months) of rheumatoid arthritis. Participants will be randomised 1:1 to web-based patient education delivered through an e-learning programme at home or standard face-to-face patient education provided at the hospital. The primary outcome is self-efficacy. Secondary outcomes are improved knowledge of rheumatoid arthritis, adherence to medication, health literacy level and quality of life. Outcomes will be measured at baseline and follow-up occurring 1, 3, 6 and 12 months after enrolment. Furthermore, data on healthcare utilisation and utilisation of the e-learning programme will be assessed at the 12-month follow-up. Statistical analysis, including differences between groups, will be evaluated using the chi-square and Kruskal–Wallis tests. Statistical analysis will follow the intention-to-treat principle, and analysis of variance will be used to evaluate the within- and between-groups differences testing the hypothesis of the ‘superiority’ of web-based patient education over standard face-to-face education provided at the hospital. Per protocol analysis will be used to assess the impact of missing data. Enrolment started in February 2021 and will end in June 2022. Discussion The study is expected to contribute to the evidence on the effectiveness of web-based patient education within rheumatic diseases. If the e-learning programme is effective, it will be incorporated into existing services to improve the self-management of patients with rheumatoid arthritis. Further, this mode of providing patient education may impact the organisation of health care for both rheumatic diseases and other chronic diseases by offering different modes of delivering patient education based on the needs and preferences of patients. Trial registration: ClinicalTrials.gov identifier NCT04669340. Registered on November 27, 2020. https://www.clinicaltrials.gov/ct2/show/NCT04669340?term=e-learning&cond=Rheumatoid+Arthritis&draw=2&rank=1. See Additional file 1 for detailed information on the dataset according to the World Health Organization Trial Registration Data Set.

Increasing power in the analysis of responder endpoints in rheumatology: a software tutorial

Background Composite responder endpoints feature frequently in rheumatology due to the multifaceted nature of many of these conditions. Current analysis methods used to analyse these endpoints discard much of the data used to classify patients as responders and are therefore highly inefficient, resulting in low power. We highlight a novel augmented methodology that uses more of the information available to improve the precision of reported treatment effects. Since these methods are more challenging to implement, we developed free, user-friendly software available in a web-based interface and as R packages. The software consists of two programs: one that supports the analysis of responder endpoints; the second that facilitates sample size estimation. We demonstrate the use of the software to conduct the analysis with both the augmented and standard analysis method using the MUSE study, a phase IIb trial in patients with systemic lupus erythematosus. Results The software outputs similar point estimates with smaller confidence intervals for the odds ratio, risk ratio and risk difference estimators using the augmented approach. The sample size required in each arm for a future trial using the novel approach based on the MUSE data is 50 versus 135 for the standard method, translating to a reduction in required sample size of approximately 63%. Conclusions We encourage trialists to use the software demonstrated to implement the augmented methodology in future studies to improve efficiency.

Vitamin D supplementation in systemic lupus erythematosus: relationship to disease activity, fatigue and the interferon signature gene expression

Background In addition to the well-known role of vitamin D in calcium homeostasis and bone metabolism, vitamin D is important in the modulation of the immune system and inflammatory processes. Vitamin D deficiency is common in patients with systemic lupus erythematosus (SLE), possibly as a result of sun avoidance. The aim of this prospective open-label study was to assess the effect of the treatment of vitamin D deficiency and insufficiency in SLE patients, particularly with regards to disease activity, fatigue and interferon signature gene expression. Methods 31 SLE patients, 13 with vitamin D deficiency and 18 with vitamin D insufficiency were treated with vitamin D3. They were supplemented with vitamin D3 8000 IU daily for 8 weeks if they were vitamin D deficient, or 8000 IU daily for 4 weeks if they were insufficient. This was followed by 2000 IU daily maintenance. They were assessed at baseline, after 6 and 12 months by means of an interview, filling in questionnaires and blood tests. The expression of 12 interferon signature genes in RNA extracted from whole blood was measured by using QuantiGene Plex technology. Results An improvement in disease activity measured by systemic lupus erythematosus disease activity index-2K (SLEDAI-2K; p = 0.028) and fatigue measured by fatigue severity scale (FSS; p = 0.071) at 12 months were noted. A significant decrease in anti-double stranded deoxyribonucleic acid (dsDNA) titre (p = 0.045) was also noted. The mean interferon signature gene expression score decreased from baseline to 6 months, however statistical significance was not achieved (p = 0.165). Conclusions Improved disease activity and fatigue have been noted when Vitamin D has been supplemented in vitamin D deficient/insufficient SLE patients. One possible mechanism could be the suppression of the interferon signature gene expression. Trial registration: The study was registered with the ISRCTN registry on 12/04/2021 (Trial ID: ISRCTN59058825).

Macrophage activation syndrome in a patient with adult-onset Still’s disease following first COVID-19 vaccination with BNT162b2

Background Adult-onset Still’s disease (AOSD) is an autoinflammatory multi-systemic syndrome. Macrophage activation syndrome (MAS) is a potentially life-threatening complication of AOSD with a mortality rate of 10–20%. Especially viral infection is thought to be a common trigger for development of MAS. On the other hand, the occurrence of MAS following vaccinations is extremely rare and has been described in a few cases after measles or influenza vaccinations and more recently after ChAdOx1 nCoV-19 (COVID-19 viral vector vaccine, Oxford-AZ). Case presentation We report the case of a twenty-year-old female with adult-onset Still’s disease (AOSD), who developed a MAS six days after receiving her first COVID-19 vaccine dose of BNT162b2 (mRNA vaccine, BioNTech/Pfizer) with ferritin levels of 136,680 µg/l (ref.: 13–150 µg/l). Conclusions To the best of our knowledge, this is the first case report of development of MAS in a patient with preexisting AOSD after vaccination in general, and SARS-CoV-2 vaccination in particular. The new mRNA vaccines have generally shown a reassuring safety profile, but it has been shown that nucleic acids in general, including mRNA can act as pathogen-associated molecular patterns that activate toll-like receptors with extensive production of pro-inflammatory cytokines and further activation of immune cells. Proving an interferon 1 response in our patient directly after vaccination, we think that in this particular case the vaccination might have acted as trigger for the development of MAS. Even if it remains difficult to establish causality in the case of rare adverse events, especially in patients with autoimmune or autoinflammatory conditions, these complications are important to monitor and register, but do not at all diminish the overwhelming positive benefit-risk ratio of licensed COVID-19 vaccines.