Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study.

Background: SARS-CoV-2 vaccination in rheumatoid arthritis (RA) patients treated with B cell-depleting drugs induced limited seroconversion but robust cellular response. We aimed to document specific T and B cell immunity in response to vaccine booster doses and breakthrough infection (BTI). Methods: We included 76 RA patients treated with rituximab who received up to four SARS-CoV-2 vaccine doses or three doses plus BTI, in addition to vaccinated healthy donors (HD) and control patients treated with tumor necrosis factor inhibitor (TNFi). We quantified anti-SARS-CoV-2 receptor-binding domain (RBD) Spike IgG, anti-nucleocapsid (NC) IgG, 92 circulating inflammatory proteins, Spike-binding B cells, and Spike-specific T cells along with comprehensive high-dimensional phenotyping and functional assays. Findings: The time since the last rituximab infusion, persistent inflammation, and age were associated with the anti-SARS-CoV-2 RBD IgG seroconversion. The vaccine-elicited serological response was accompanied by an incomplete induction of peripheral Spike-specific memory B cells but occurred independently of T cell responses. Vaccine- and BTI-elicited cellular immunity was similar between RA and HD ex vivo in terms of frequency or phenotype of Spike-specific cytotoxic T cells and in vitro in terms of the functionality and differentiation profile of Spike-specific T cells. Interpretation: SARS-CoV-2 vaccination in RA can induce persistent effector T-cell responses that are reactivated by BTI. Paused rituximab medication allowed serological responses after a booster dose (D4), especially in RA with lower inflammation, enabling efficient humoral and cellular immunity after BTI, and contributed overall to the development of potential durable immunity.

Modifiable prognostic factors of high societal costs among people on sick leave due to musculoskeletal disorders: findings from an occupational cohort study.

OBJECTIVES: The objective was to identify modifiable prognostic factors of high societal costs among people on sick leave due to musculoskeletal disorders, and to identify modifiable prognostic factors of high costs related to separately healthcare utilisation and productivity loss. DESIGN: A prospective cohort study with a 1-year follow-up. PARTICIPANTS AND SETTING: A total of 549 participants (aged 18-67 years) on sick leave (≥ 4 weeks) due to musculoskeletal disorders in Norway were included. OUTCOME MEASURES AND METHOD: The primary outcome was societal costs aggregated for 1 year of follow-up and dichotomised as high or low, defined by the top 25th percentile. Secondary outcomes were high costs related to separately healthcare utilisation and productivity loss aggregated for 1 year of follow-up. Healthcare utilisation was collected from public records and included primary, secondary and tertiary healthcare use. Productivity loss was collected from public records and included absenteeism, work assessment allowance and disability pension. Nine modifiable prognostic factors were selected based on previous literature. Univariable and multivariable binary logistic regression analyses were performed to identify associations (crude and adjusted for selected covariates) between each modifiable prognostic factor and having high costs. RESULTS: Adjusted for selected covariates, six modifiable prognostic factors associated with high societal costs were identified: pain severity, disability, self-perceived health, sleep quality, return to work expectation and long-lasting disorder expectation. Depressive symptoms, work satisfaction and health literacy showed no prognostic value. More or less similar results were observed when high costs were related to separately healthcare utilisation and productivity loss. CONCLUSION: Factors identified in this study are potential target areas for interventions which could reduce high societal costs among people on sick leave due to musculoskeletal disorders. However, future research aimed at replicating these findings is warranted. TRIAL REGISTRATION NUMBER: NCT04196634, 12 December 2019.

EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis: 2023 update.

INTRODUCTION: Hip and knee osteoarthritis (OA) are increasingly common with a significant impact on individuals and society. Non-pharmacological treatments are considered essential to reduce pain and improve function and quality of life. EULAR recommendations for the non-pharmacological core management of hip and knee OA were published in 2013. Given the large number of subsequent studies, an update is needed. METHODS: The Standardised Operating Procedures for EULAR recommendations were followed. A multidisciplinary Task Force with 25 members representing 14 European countries was established. The Task Force agreed on an updated search strategy of 11 research questions. The systematic literature review encompassed dates from 1 January 2012 to 27 May 2022. Retrieved evidence was discussed, updated recommendations were formulated, and research and educational agendas were developed. RESULTS: The revised recommendations include two overarching principles and eight evidence-based recommendations including (1) an individualised, multicomponent management plan; (2) information, education and self-management; (3) exercise with adequate tailoring of dosage and progression; (4) mode of exercise delivery; (5) maintenance of healthy weight and weight loss; (6) footwear, walking aids and assistive devices; (7) work-related advice and (8) behaviour change techniques to improve lifestyle. The mean level of agreement on the recommendations ranged between 9.2 and 9.8 (0-10 scale, 10=total agreement). The research agenda highlighted areas related to these interventions including adherence, uptake and impact on work. CONCLUSIONS: The 2023 updated recommendations were formulated based on research evidence and expert opinion to guide the optimal management of hip and knee OA.

Effect of high-intensity interval training in physiotherapy primary care for patients with inflammatory arthritis: the ExeHeart randomised controlled trial.

OBJECTIVES: To assess the effect of high-intensity interval training (HIIT) delivered in physiotherapy primary care on the primary outcome of cardiorespiratory fitness (CRF) in patients with inflammatory arthritis (IA). Additionally, to explore the effects of HIIT on secondary outcomes, including cardiovascular disease (CVD) risk factors and disease activity. METHODS: Single-blinded randomised controlled trial with 60 patients randomly assigned to either a control group receiving usual care or an exercise group receiving usual care and 12 weeks of individualised HIIT at 90%-95% peak heart rate. Outcomes were assessed at baseline, 3 months and 6 months post baseline and included CRF measured as peak oxygen uptake (VO2peak), classic CVD risk factors, disease activity, anthropometry and patient-reported physical activity, pain, fatigue, disease impact and exercise beliefs and self-efficacy. RESULTS: Intention-to-treat analysis demonstrated a significant between-group difference in VO2peak at 3 months (2.5 mL/kg/min, 95% CI 0.9 to 4.0) and 6 months (2.6 mL/kg/min, 95% CI 0.8 to 4.3) in favour of the exercise group. A beneficial change in self-reported physical activity in favour of the exercise group was observed at 3 and 6 months. The HIIT intervention was well-tolerated with minimal adverse events and no apparent impact on disease activity. Differences in secondary outcomes related to CVD risk factors, disease impact, pain, fatigue and exercise beliefs and self-efficacy were generally small and non-significant. CONCLUSION: After 12 weeks of supervised HIIT delivered in physiotherapy primary care, patients with IA demonstrated a favourable improvement in CRF, with sustained effects at 6-month follow-up. TRIAL REGISTRATION NUMBER: NCT04922840.

Follow-Up of Patients With Axial Spondyloarthritis in Specialist Health Care With Remote Monitoring and Self-Monitoring Compared With Regular Face-to-Face Follow-Up Visits (the ReMonit Study): Protocol for a Randomized, Controlled Open-Label Noninferiority Trial.

BACKGROUND: Patients with chronic inflammatory joint diseases such as axial spondyloarthritis have traditionally received regular follow-up in specialist health care to maintain low disease activity. The follow-up has been organized as prescheduled face-to-face visits, which are time-consuming for both patients and health care professionals. Technology has enabled the remote monitoring of disease activity, allowing patients to self-monitor their disease and contact health care professionals when needed. Remote monitoring or self-monitoring may provide a more personalized follow-up, but there is limited research on how these follow-up strategies perform in maintaining low disease activity, patient satisfaction, safety, and cost-effectiveness. OBJECTIVE: The Remote Monitoring in Axial Spondyloarthritis (ReMonit) study aimed to assess the effectiveness of digital remote monitoring and self-monitoring in maintaining low disease activity in patients with axial spondyloarthritis. METHODS: The ReMonit study is a 3-armed, single-site, randomized, controlled, open-label noninferiority trial including patients with axial spondyloarthritis with low disease activity (Ankylosing Spondylitis Disease Activity Score <2.1) and on stable treatment with a tumor necrosis factor inhibitor. Participants were randomized 1:1:1 to arm A (usual care, face-to-face visits every sixth month), arm B (remote monitoring, monthly digital registration of patient-reported outcomes), or arm C (patient-initiated care, self-monitoring, no planned visits during the study period). The primary end point was disease activity measured with the Ankylosing Spondylitis Disease Activity Score, evaluated at 6, 12, and 18 months. We aimed to include 240 patients, 80 in each arm. Secondary end points included other measures of disease activity, patient satisfaction, safety, and cost-effectiveness. RESULTS: The project is funded by the South-Eastern Norway Regional Health Authority and Centre for the treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Norway. Enrollment started in September 2021 and was completed with 242 patients by June 2022. The data collection will be completed in December 2023. CONCLUSIONS: To our knowledge, this trial will be among the first to evaluate the effectiveness, safety, and cost-effectiveness of remote digital monitoring and self-monitoring of patients with axial spondyloarthritis compared with usual care. Hence, the ReMonit study will contribute important knowledge to personalized follow-up strategies for patients with axial spondyloarthritis. These results may also be relevant for other patient groups with inflammatory joint diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT05031767; hpps://www.clinicaltrials.gov/study/NCT05031767. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52872.

Willingness, perceived facilitators and barriers to use remote care among healthcare professionals - a cross-sectional study.

BACKGROUND: Remote care has the potential of improving access to timely care for people with inflammatory joint diseases (IJD), but there is limited knowledge on how this approach is regarded by healthcare professionals (HCP). This study aimed to examine willingness, perceived facilitators, and barriers to use remote care among HCP. METHODS: Employees at 20 rheumatology departments in Norway received a digital survey containing 16 statements regarding willingness, perceived facilitators and barriers to use remote care. Statements were scored using numeric rating scales (NRS, 0-10, 10 = strongly agree), and analysed in linear regression models. Open-ended responses with participant-defined facilitators and barriers were analysed using qualitative manifest analysis. RESULTS: A total of 130 participants from 17 departments completed the survey. The majority of participants were 45 years or older (n = 84, 54%), 54 (42%) were medical doctors, 48 (37%) nurses, and 27 (21%) were allied healthcare professionals, clinical leaders, or secretaries. A high willingness to use remote care was observed (median NRS: 9, IQR 8-10). The facilitator statement with the highest score was that patients save time and costs by using remote care, whereas the barrier statement with the highest score was the lack of physical examination. Willingness to use remote care was positively associated with the belief that patients wish to use it (ß: 0.18, 95% CI: 0.00, 0.34), that patients in remission need less hospital visits (ß: 0.30, 95% CI: 0.16, 0.43), and if remote care is widely adopted by co-workers (ß: 0.27, 95% CI: 0.15, 0.39). Willingness was negatively associated with mistrust in the technical aspects of remote care (ß: -0.26, 95% CI:-0.40, -0.11), and lack of physical examination (ß: -0.24, 95% CI: -0.43, -0.06). The open-ended responses showed that technological equipment, eligible patients, user-friendly software, adequate training and work flow could be facilitators, but also that lack of these factors were considered barriers to use remote care. CONCLUSION: This study showed that HCP have a high willingness to use remote care, and provides important new knowledge on perceived facilitators and barriers among HCP relevant for implementation of remote care for eligible patients with IJD.

Criterion Validity and Responsiveness of Estimated Cardiorespiratory Fitness Models in Patients with Inflammatory Joint Disease.

Cardiorespiratory fitness (CRF) is an excellent marker of overall health. This study aimed to assess criterion validity and responsiveness of estimated CRF models (eCRF) in patients with inflammatory joint disease (IJD). CRF was measured directly as peak oxygen uptake (VO2peak) by a Cardiopulmonary Exercise Test (CPET), while one generic eCRF model (eCRFGEN) and two disease-specific eCRF models (eCRFALT and eCRFPGA) were used to estimate CRF at baseline and after 3 months in 55 Norwegian patients with IJD. Moderate correlations were observed between eCRFGEN, eCRFALT, eCRFPGA, and VO2peak at baseline (ICC 0.60, 0.64 and 0.62, respectively) and 3 months (ICC 0.62, 0.65 and 0.57, respectively). All eCRF models overestimated measured VO2peak, and there was large variability in agreement of individual measurements at baseline and at 3 months. Weak correlations were observed for responsiveness of eCRFGEN (ICC 0.39), eCRFALT (ICC 0.40) and eCRFPGA (ICC 0.39). Mean differences between change in eCRF models and change in VO2peak were small, but the wide limits of agreement exceeded the pre-defined clinically acceptable margins. The eCRF models possessed adequate ability to detect ≥3.5 mL/kg/min improvement in VO2peak. eCRF may suffice for group-level assessment, but caution is advised when applying eCRF to individual patients with IJD.

Adherence to a Web-based Exercise Programme: A Feasibility Study Among Patients with Hip or Knee Osteoarthritis.

OBJECTIVES: To describe adherence to a 12-week web-based aerobic exercise programme, to compare characteristics between those who adhere or not, and to identify barriers for exercising in patients with hip or knee osteoarthritis. DESIGN: Single-arm feasibility study. SUBJECTS: Patients with hip or knee osteoarthritis in specialist healthcare, age 40-80 years, and not candidates for joint surgery. METHODS: Adherence to a 12-week exercise programme was defined as having completed ≥ 2 exercise sessions a week for at least 8 weeks. Baseline differences between adherent and non-adherent groups in demographics, symptoms, disability, physical activity and fitness were assessed using Mann-Whitney U or χ2 tests. Reasons for not completing exercise sessions were reported in weekly diaries.  Results: A total of 29 patients (median age 64 years, 72% female) were included. Median baseline pain (numerical rating scale 0-10) was 5. Fifteen patients adhered to the exercise programme, 14 did not. Non-adherent patients were less active (p = 0.032) and had lower cardiorespiratory fitness (p = 0.031). The most frequently reported barrier to exercising was sickness. Less than 10% reported pain as a barrier. CONCLUSION: Half of the patients with hip or knee osteoarthritis adhered to the digitally delivered exercise programme and the most frequently reported barrier for adherence was sickness, while less than 10% reported pain as a reason for not exercising. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04084834. The Regional Committee for Medical and Health Research Ethics South-East, 2018/2198.

Digitally delivered education and exercises for patients with hand osteoarthritis-An observational study.

Hand osteoarthritis (OA) is a common form of OA, for which education and exercise are considered the first-line treatment. The aim of the present study was to examine pain and perceived hand function in participants following 3 months of digitally delivered first-line treatment for hand OA. Three-hundred-and-seventy-nine of 846 participants with clinical signs and symptoms of hand OA completed the study. The digital hand OA treatment program consists of video instructed daily exercises and patient education through text lessons. Pain (NRS, 0 no pain, 10 worst) was the primary outcome, and stiffness (NRS) and the Functional Index for Hand OsteoArthritis (FIHOA, 0 best, 30 worst) were among secondary outcomes. The McNemar test and linear mixed effect regression model were used to assess the changes in outcomes from baseline to 3-month. After three months, the digitally delivered program was associated with a significant decrease in pain intensity (mean change -1.30 (95% CI -1.49, -1.12)) and hand stiffness (mean change -0.81 (95% CI -1.02, -0.60)) but no conclusive changes in the FIHOA scores (mean change 0.3 (95% CI -0.2, 0.7)). The results agree with reports on face-to-face delivered first-line treatment for hand OA suggesting that digital treatment is a viable treatment option in patients with hand OA.

Is multimodal occupational therapy in addition to usual care cost-effective in people with thumb carpometacarpal osteoarthritis? A cost-utility analysis of a randomised controlled trial.

OBJECTIVE: The aim was to evaluate the cost-utility of a 3-month multimodal occupational therapy intervention in addition to usual care in patients with thumb carpometacarpal osteoarthritis (CMC1 OA). METHODS: A cost-utility analysis was performed alongside a multicentre randomised controlled trial including three rheumatology departments in Norway. A total of 180 patients referred to surgical consultation due to CMC1 OA were randomised to either multimodal occupational therapy including patient education, hand exercises, assistive devices and orthoses (n=90), or usual care receiving only information on OA (n=90). The outcome measure was quality-adjusted life-years (QALYs) derived from the generic questionnaire EQ-5D-5L over a 2-year period. Resource use and health-related quality of life of the patients were prospectively collected at baseline, 4, 18 and 24 months. Costs were estimated by taking a healthcare and societal perspective. The results were expressed as incremental cost-effectiveness ratios, and a probabilistic sensitivity analysis with 1000 replications following intention-to-treat principle was done to account for uncertainty in the analysis. RESULTS: During the 2-year follow-up period, patients receiving multimodal occupational therapy gained 0.06 more QALYs than patients receiving usual care. The mean (SD) direct costs were €3227 (3546) in the intervention group and €4378 (5487) in the usual care group, mean difference €-1151 (95% CI -2564, 262). The intervention was the dominant treatment with a probability of 94.5% being cost-effective given the willingness-to-pay threshold of €27 500. CONCLUSIONS: The within-trial analysis demonstrated that the multimodal occupational therapy in addition to usual care was cost-effective at 2 years in patients with CMC1 OA. TRIAL REGISTRATION NUMBER: NCT01794754.

Associations between cardiovascular risk factors, disease activity and cardiorespiratory fitness in patients with inflammatory joint disease: a cross-sectional analysis.

BACKGROUND: Inflammatory joint diseases (IJD) are accompanied by an increased risk of cardiovascular disease (CVD). Cardiorespiratory fitness (CRF) is a modifiable CVD risk factor and low levels of CRF associate with an elevated CVD risk. This study aimed to investigate the associations between CVD risk factors, disease activity and CRF in patients with IJD and to explore differences between patients with normal versus low levels of CRF. METHODS: CRF was measured as peak oxygen uptake (VO2peak) with a cardiopulmonary exercise test. Participants were also evaluated for: Body composition, blood pressure, blood lipids, inflammatory markers and disease activity. Patient-reported use of cigarettes/snuff, medication, disease duration, pain, fatigue, CVD history, habitual physical activity and exercise beliefs and self-efficacy were collected by questionnaire. Cross-sectional associations between CVD risk factors, disease-related factors and CRF were analyzed by multiple linear regression. CRF was categorized to normal CRF (VO2peak ≥ 80%) or low CRF (VO2peak < 80%) according to age- and gender-stratified reference data. Differences in demographic, CVD and disease-related factors between patients with normal versus low CRF were explored. RESULTS: In 60 Norwegian patients with IJD [34 females, age 59 years (IQR: 52-63)], mean VO2peak was 30.2 (± 6.9) mL/kg/min, corresponding to 83% (± 18) of normative reference values. Age (coefficient: - 0.18 years, p = 0.01) and fat mass (coefficient: - 0.67 %, p < 0.001) were inversely associated with CRF, while physical activity index (coefficient: 0.13 points, p = 0.05) was positively associated with CRF (R2 = 0.66). There were no significant associations between CRF, classical CVD risk factors and disease-related variables. Compared to patients with low CRF (n = 30), patients with normal CRF (n = 30) had higher peak oxygen uptake (+ 9.4 mL/kg/min, p < 0.001), high-density lipoprotein cholesterol (+ 0.5 mmol L-1, p < 0.001), and exercise self-efficacy (+ 6.9, p < 0.01) as well as lower fat mass (- 8.7%, p < 0.001), resting heart rate (- 8.0 beats/min, p < 0.01) and triglycerides (- 0.5 mmol L-1, p < 0.01). CONCLUSIONS: In this sample of IJD-patients, age, fatmass and physical activity level were associated with CRF. CRF was lower than reference values and patients with normal CRF presented with a more favorable health profile. There is a continued need for exercise interventions to improve CRF in patients with IJD. TRIAL REGISTRATION: NCT04922840.

Mechanisms of vocational interventions for return to work from musculoskeletal conditions: a mediation analysis of the MI-NAV trial.

OBJECTIVES: To investigate whether and to what extent, return to work (RTW) expectancy and workability mediate the effect of two vocational interventions on reducing sickness absence in workers on sick leave from a musculoskeletal condition. METHODS: This is a preplanned mediation analysis of a three-arm parallel randomised controlled trial which included 514 employed working adults with musculoskeletal conditions on sick leave for at least 50% of their contracted work hours for ≥7 weeks. Participants were randomly allocated (1:1:1) to one of three treatment arms; usual case management (UC) (n=174), UC plus motivational interviewing (MI) (n=170) and UC plus a stratified vocational advice intervention (SVAI) (n=170). The primary outcome was the number of sickness absence days over 6 months from randomisation. Hypothesised mediators included RTW expectancy and workability assessed 12 weeks after randomisation. RESULTS: The mediated effect of the MI arm compared with UC on sickness absence days through RTW expectancy was -4.98 days (-8.89 to -1.04), and workability was -3.17 days (-8.55 to 2.32). The mediated effect of the SVAI arm compared with UC on sickness absence days through RTW expectancy was -4.39 days (-7.60 to -1.47), and workability was -3.21 days (-7.90 to 1.50). The mediated effects for workability were not statistically significant. CONCLUSIONS: Our study provides new evidence for the mechanisms of vocational interventions to reduce sickness absence related to sick leave due to musculoskeletal conditions. Changing an individual's expectation that RTW is likely may result in meaningful reductions in sickness absence days. TRIAL REGISTRATION NUMBER: NCT03871712.

Effectiveness of adding motivational interviewing or a stratified vocational advice intervention to usual case management on return to work for people with musculoskeletal disorders: the MI-NAV randomised controlled trial.

OBJECTIVES: To evaluate if adding motivational interviewing (MI) or a stratified vocational advice intervention (SVAI) to usual case management (UC), reduced sickness absence over 6 months for workers on sick leave due to musculoskeletal disorders. METHODS: We conducted a three-arm parallel pragmatic randomised controlled trial including 514 employed workers (57% women, median age 49 (range 24-66)), on sick leave for at least 50% of their contracted work hours for ≥7 weeks. All participants received UC. In addition, those randomised to UC+MI were offered two MI sessions from social insurance caseworkers and those randomised to UC+SVAI were offered vocational advice from physiotherapists (participants with low/medium-risk for long-term sickness absence were offered one to two sessions, and those with high-risk were offered three to four sessions). RESULTS: Median sickness absence was 62 days, (95% CI 52 to 71) in the UC arm (n=171), 56 days (95% CI 43 to 70) in the UC+MI arm (n=169) and 49 days (95% CI 38 to 60) in the UC+SVAI arm (n=169). After adjusting for predefined potential confounding factors, the results showed seven fewer days in the UC+MI arm (95% CI -15 to 2) and the UC+SVAI arm (95% CI -16 to 1), compared with the UC arm. The adjusted differences were not statistically significant. CONCLUSIONS: The MI-NAV trial did not show effect on return to work of adding MI or SVAI to UC. The reduction in sickness absence over 6 months was smaller than anticipated, and uncertain due to wide CIs. TRIAL REGISTRATION NUMBER: NCT03871712.

Identification and Characterisation of Trajectories of Sickness Absence Due to Musculoskeletal Pain: A 1-Year Population-based Study.

Purpose This study aimed to identify trajectories of sickness absence in workers on sick leave due to musculoskeletal disorders and explore the association between these trajectories and established prognostic factors for sickness absence. Methods We conducted a prospective cohort study of 549 workers (56% women, aged 18-67 years) on sick leave due to musculoskeletal disorders in Norway in 2018-2019. Sickness absence data were collected from the Norwegian sick leave registry and prognostic factors via self-reported baseline questionnaires. We used group-based trajectory modelling to define the different trajectories of sickness absence spanning a 1-year period. Multivariable multinomial logistic regression was used to estimate odds ratios and 95% confidence intervals for prognostic factors associated with the identified trajectory groups. Results We identified six distinct trajectories of sickness absence over 1 year: 'fast decrease' (27% of the cohort): 'moderate decrease' (22%); 'slow decrease' (12%); 'u-shape' (7%); 'persistent moderate' (13%); and 'persistent high' (18%). Prognostic factors, such as previous sickness absence days, return-to-work expectancy, workability, multisite pain, and health scores, differentiated between the sickness absence trajectories (all P < 0.05). Negative return-to-work expectancy was associated with the three trajectory groups with the highest number of sickness absence days ('slow decrease', 'persistent moderate', and 'persistent high'). Conclusions This is the first study to explore the association of return-to-work expectancy with trajectories of sickness absence. Our findings highlight different patterns of sickness absence and the complex range of prognostic factors. These findings have implications for secondary and tertiary prevention strategies for work absence in workers with musculoskeletal disorders.

Immunogenicity and safety of a three-dose SARS-CoV-2 vaccination strategy in patients with immune-mediated inflammatory diseases on immunosuppressive therapy.

OBJECTIVES: Humoral vaccine responses to SARS-CoV-2 vaccines are impaired and short lasting in patients with immune-mediated inflammatory diseases (IMID) following two vaccine doses. To protect these vulnerable patients against severe COVID-19 disease, a three-dose primary vaccination strategy has been implemented in many countries. The aim of this study was to evaluate humoral response and safety of primary vaccination with three doses in patients with IMID. METHODS: Patients with IMID on immunosuppressive therapy and healthy controls receiving three-dose and two-dose primary SARS-CoV-2 vaccination, respectively, were included in this prospective observational cohort study. Anti-Spike antibodies were assessed 2-4 weeks, and 12 weeks following each dose. The main outcome was anti-Spike antibody levels 2-4 weeks following three doses in patients with IMID and two doses in controls. Additional outcomes were the antibody decline rate and adverse events. RESULTS: 1100 patients and 303 controls were included. Following three-dose vaccination, patients achieved median (IQR) antibody levels of 5720 BAU/mL (2138-8732) compared with 4495 (1591-6639) in controls receiving two doses, p=0.27. Anti-Spike antibody levels increased with median 1932 BAU/mL (IQR 150-4978) after the third dose. The interval between the vaccine doses and vaccination with mRNA-1273 or a combination of vaccines were associated with antibody levels following the third dose. Antibody levels had a slower decline-rate following the third than the second vaccine dose, p<0.001. Adverse events were reported by 464 (47%) patients and by 196 (78%) controls. Disease flares were reported by 70 (7%) patients. CONCLUSIONS: This study shows that additional vaccine doses to patients with IMID contribute to strong and sustained immune-responses comparable to healthy persons vaccinated twice, and supports repeated vaccination of patients with IMID. TRIAL REGISTRATION NUMBER: NCT04798625.

The persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses in patients on immunosuppressive therapy compared to healthy controls-a prospective cohort study.

BACKGROUND: The durability of vaccine-induced humoral immunity against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy is not known. The aim of this study was to compare the persistence of anti-Spike antibodies following two-dose SARS-CoV-2 vaccination between IMID patients and healthy controls and to identify factors associated with antibody decline. METHODS: IMID patients on immunosuppressive medication enrolled in the prospective observational Nor-vaC study were included. Participants received two-dose SARS-CoV-2 vaccination. Serum collected at two time points following vaccination (first assessment within 6-48 days, second within 49-123 days) were analyzed for antibodies binding the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. Multivariable regression models estimated percent reduction in anti-RBD over 30 days and factors associated with reduction. RESULTS: A total of 1108 patients (403 rheumatoid arthritis, 195 psoriatic arthritis, 195 spondyloarthritis, 124 ulcerative colitis, 191 Crohn's disease) and 134 controls provided blood samples within the defined intervals (median 19 days [IQR 15-24] and 97 days [87-105] after second vaccine dose). Antibody levels were lower in patients compared to controls at both time points, with median anti-RBD 2806 BAU/ml [IQR 1018-6068] in patients and 6187 BAU/ml [4105-7496] in controls (p<0.001) at first assessment, and 608 BAU/ml [IQR 58-1053] in patients and 1520 BAU/ml [979-3766] in controls (p<0.001) at second assessment. At second assessment, low anti-RBD antibody levels (defined as <200 BAU/ml) were found in 449 (41%) patients, and 6 (5%) controls (p<0.001). The change was - 83% in patients and - 66% in controls (p<0.001). Patients had a greater estimated 30 days percent reduction in anti-RBD levels compared to controls - 4.9 (95% CI - 7.4 to - 2.4), (p<0.05). Among therapies, mono- or combination treatment with tumor necrosis factor inhibitors was associated with the greatest decline. CONCLUSIONS: Within 4 months after vaccination, antibody levels declined considerably in both IMID patients and controls. Patients had lower initial antibody levels and a more pronounced decline compared to healthy controls and were therefore more likely to decline to low antibody levels. These results support that IMID patients need additional vaccine doses at an earlier stage than healthy individuals.

Effect of a mHealth exercise intervention compared with supervised exercise therapy in osteoarthritis management: protocol of the DigiOA trial.

INTRODUCTION: Soaring prevalence of hip and knee osteoarthritis (OA) inflicts high costs on the healthcare system. A further rise in the OA incidence is expected, generating increased demand of care potentially challenging accessibility and threatening to overwhelm the healthcare system. Innovative solutions that may improve accessibility to recommended OA care for patients in primary care and maintain healthcare sustainability are warranted. Digitalising home exercise therapy may be one such solution. The primary aim of this study is to evaluate the effectiveness of a mobile health app providing digitalised home exercises, compared with supervised exercise therapy in patients with OA. Second, we will evaluate the cost-efficiency of the intervention and explore potential differences in outcome and adherence to exercises in the experimental treatment group. METHODS AND ANALYSIS: A two-armed non-inferiority randomised controlled trial will be conducted. In total, 156 patients with hip and/or knee OA will be recruited from physiotherapy clinics in primary care in Norway. Following patient education, patients will be randomised to either 6 weeks of standard treatment (2 weekly sessions of supervised exercise therapy) or experimental treatment (home exercises via the Virtual Training (VT) app). Primary outcome is the proportion of Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responders at 6 weeks. Secondary outcomes include physical performance, patient-reported outcomes related to pain, fatigue, disease activity, physical function, mental health, health related quality of life, self-efficacy, utilisation of healthcare services and medication, digital competence and use of apps. ETHICS AND DISSEMINATION: Patients will sign an informed consent form before participating in the trial. Approval has been granted by the Regional Ethics Committee (201105) and Data Protection Officer at Diakonhjemmet Hospital (00221). Patient research partners will contribute in all parts of the study. TRIAL REGISTRATION NUMBER: NCT04767854.

The AktiWeb study: feasibility of a web-based exercise program delivered by a patient organisation to patients with hip and/or knee osteoarthritis.

BACKGROUND: Patient organisations may be an under-utilised resource in follow-up of patients requiring long-term exercise as part of their disease management. The purpose of this study was to explore the feasibility of a web-based exercise program delivered by a patient organisation to patients with hip and/or knee osteoarthritis (OA). METHODS: In this pre-post feasibility study, patients aged 40-80 years with hip and/or knee OA were recruited from Diakonhjemmet Hospital. The 12-week intervention was delivered through a patient organisation's digital platform. Feasibility was evaluated by proportion of eligible patients enrolled, proportion of enrolled patients who provided valid accelerometer data at baseline, and proportion completing the cardiorespiratory exercise test according to protocol at baseline and completed follow-up assessments. Patient acceptability was evaluated for website usability, satisfaction with the initial exercise level and comprehensibility of the exercise program. Change in clinical outcomes were assessed for physical activity, cardiorespiratory fitness and patient-reported variables. RESULTS: In total, 49 eligible patients were identified and 35 were enrolled. Thirty (86%) of these attended baseline assessments and provided valid accelerometer data and 18 (51%) completed the maximal cardiorespiratory exercise test according to protocol. Twenty-two (63%) patients completed the follow-up questionnaire, and they rated the website usability as 'acceptable' [median 77.5 out of 100 (IQR 56.9, 85.6)], 19 (86%) reported that the initial exercise level was 'just right' and 18 (82%) that the exercise program was 'very easy' or 'quite easy' to comprehend. Improvement in both moderate to vigorous physical activity (mean change 16.4 min/day; 95% CI 6.9 to 25.9) and cardiorespiratory fitness, VO2peak (mean change 1.83 ml/kg/min; 95% CI 0.29 to 3.36) were found in a subgroup of 8 patients completing these tests. Across all patient-reported outcomes 24-52% of the patients had a meaningful improvement (n = 22). CONCLUSION: A web-based exercise program delivered by a patient organisation was found to be feasible and acceptable in patients with hip and/or knee OA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04084834 (registered 10 September 2019). The Regional Committee for Medical and Health Research Ethics south-east, 2018/2198. URL: Prosjekt #632074 - Aktiv med web-basert støtte. - Cristin (registered 7 June 2019).

Prevalence of Antenatal Depressive Symptoms and its Associated Factors among Pregnant Nepalese Women with and Without Low Back- and/or Pelvic Girdle Pain.

BACKGROUND: Pregnant women with health problems have shown higher odds of depressive symptoms. Evidence suggests a co-morbid relation between pregnancy-related low back pain and/or pelvic girdle pain and the risk of depression. The aims were to investigate the prevalence of symptoms of depression among pregnant Nepalese women in general and among pregnant Nepalese women with low back pain and/or pelvic girdle pain and to identify factors associated to symptoms of depression. METHODS: A cross-sectional study using standardized condition-specific questionnaires with response from 1284 pregnant Nepalese women. Multivariate logistic regression analysis determined variables associated with symptoms of depression. RESULTS: Twenty-one percent of the women presented with moderate to high symptom level of depression, compared to 29% of the women with low back pain and/or pelvic girdle pain. Low education, living without husband, no rest during work, higher self-reported disability, higher pain intensity and symptoms of pelvic organ prolapse were associated with higher odds of symptoms of depression among the women with low back pain and/or pelvic girdle pain. For the total sample, fetching water and having symptoms of low back pain and/or pelvic girdle pain and living without husband were associated to symptoms of depression. CONCLUSIONS: Twenty-one percent of the pregnant women reported moderate to high symptom level of depression. The proportion of women with symptoms of depression was significantly higher among the women categorized as having low back pain and/or pelvic girdle pain. Our findings highlight the need to address both emotional and physical needs among pregnant Nepalese women.