A trial-based economic evaluation of the CaFaSpA referral strategy for axial spondyloarthritis.

OBJECTIVE: To assess the cost-utility from healthcare and societal perspectives of the digital CaFaSpA referral strategy (CS) for axial spondyloarthritis (axSpA) in primary care patients with chronic low back pain (CLBP). METHOD: A cluster randomized controlled trial was performed in the Netherlands. General practice units were randomized into CS or usual care (UC). Economic evaluation was performed from the healthcare and societal perspectives within a 12-month time horizon. Outcome measures encompassed disability [Roland-Morris Disability Questionnaire (RMDQ)] and health-related quality of life (EQ-5D-3L). Direct medical (iMTA Medical Consumption Questionnaire) and indirect costs (iMTA Productivity Cost Questionnaire), including productivity loss, were evaluated. Incremental cost-utility ratios (ICURs) were calculated. RESULTS: The study included 90 GP clusters with 563 patients (CS: n = 260; UC: n = 303) (mean ± sd age 36.3 ± 7.5 years; 66% female). After 12 months, no minimal important differences in outcomes were observed for RMDQ (-0.21, 95%CI -1.52 to 1.13) or EQ-5D (-0.02, 95%CI -0.08 to 0.05). However, total costs were significantly lower in the CS group owing to lower productivity loss costs. The ICUR for RMDQ was €18,059 per point decrease and €220,457 per quality-adjusted life year increase. CONCLUSIONS: Digital referral did not decrease the overall healthcare status of patients after 1 year of follow-up and appears to be more cost-effective than UC. Therefore, CS can be used as an appropriate primary care referral model for CLBP patients at risk for axSpA. This will accelerate timely provision of care by the right caregiver.

PROMISE: effect of protein supplementation on fat-free mass preservation after bariatric surgery, a randomized double-blind placebo-controlled trial.

INTRODUCTION: Protein malnutrition after bariatric surgery is a severe complication and leads to significant morbidity. Previous studies have shown that protein intake and physical activity are the most important factors in the preservation of fat-free mass during weight loss. Low protein intake is very common in patients undergoing bariatric surgery despite dietary counseling. Protein powder supplements might help patients to achieve the protein intake recommendations after bariatric surgery and could therefore contribute to preserve fat-free mass. This double-blind randomized placebo-controlled intervention study aims to assess the effect of a daily consumed clear protein powder shake during the first 6 months after bariatric surgery on fat-free mass loss in the first 12 months after laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS AND ANALYSIS: Inclusion will take place at the outpatient clinic of the bariatric expertise center for obesity of the Maasstad Hospital. Patients will be randomly assigned to either the intervention or control group before surgery. The intervention group will receive a clear protein powder shake of 200 ml containing 20 g of whey protein dissolved in water which should be taken daily during the first 6 months after LRYGB on top of their normal postoperative diet. The control group will receive an isocaloric, clear, placebo shake containing maltodextrine. Postoperative rehabilitation and physiotherapeutical guidance will be standardized and similar in both groups. Also, both groups will receive the same dietary advice from specialized dieticians. The main study parameter is the percentage of fat-free mass loss 6 months after surgery, assessed by multi-frequency bioelectrical impedance analysis (MF-BIA). ETHICS AND DISSEMINATION: The protocol, version 2 (February 20, 2022) has been approved by the Medical Research Ethics Committees United (MEC-U) (NL 80414.100.22). The results of this study will be submitted to peer-reviewed journals. TRIAL REGISTRATION: ClinicalTrials.gov NCT05570474. Registered on October 5, 2022.

Arthroscopic synovectomy versus intra-articular injection of corticosteroids for the management of refractory psoriatic or rheumatoid arthritis of the wrist: study protocol for a randomized controlled trial (ARCTIC trial).

BACKGROUND: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint destruction if inadequately treated. Standard care consists primarily of disease-modifying anti-rheumatic drugs (DMARDs), often supported by systemic corticosteroids or intra-articular corticosteroid injections (IACSI). IACSI, despite their use worldwide, show poor response in a substantial group of patients. Arthroscopic synovectomy of the wrist is the surgical removal of synovitis with the goal to relieve pain and improve wrist function. The primary objective of this study is to evaluate wrist function following arthroscopic synovectomy compared to IACSI in therapy-resistant patients with rheumatoid or psoriatic arthritis. Secondary objectives include radiologic progress, disease activity, health-related quality of life, work participation and cost-effectiveness during a 1-year follow-up. METHODS: This protocol describes a prospective, randomized controlled trial. RA and PsA patients are eligible with prominent wrist synovitis objectified by a rheumatologist, not responding to at least 3 months of conventional DMARDs and naïve to biological DMARDs. For 90% power, an expected loss to follow-up of 5%, an expected difference in mean Patient-Rated Wrist Evaluation score (PRWE, range 0-100) of 11 and α = 0.05, a total sample size of 80 patients will be sufficient to detect an effect size. Patients are randomized in a 1:1 ratio for arthroscopic synovectomy with deposition of corticosteroids or for IACSI. Removed synovial tissue will be stored for an ancillary study on disease profiling. The primary outcome is wrist function, measured with the PRWE score after 3 months. Secondary outcomes include wrist mobility and grip strength, pain scores, DAS28, EQ-5D-5L, disease progression on ultrasound and radiographs, complications and secondary treatment. Additionally, a cost-effectiveness analysis will be performed, based on healthcare costs (iMCQ questionnaire) and productivity loss (iPCQ questionnaire). Follow-up will be scheduled at 3, 6 and 12 months. Patient burden is minimized by combining study visits with regular follow-ups. DISCUSSION: Persistent wrist arthritis continues to be a problem for patients with rheumatic joint disease leading to disability. This is the first randomized controlled trial to evaluate the effect, safety and feasibility of arthroscopic synovectomy of the wrist in these patients compared to IACSI. TRIAL REGISTRATION: Dutch trial registry (CCMO), NL74744.100.20. Registered on 30 November 2020. CLINICALTRIALS: gov NCT04755127. Registered after the start of inclusion on 15 February 2021.

Impact of triage by a rheumatologist on appropriateness of referrals from primary to secondary care: a cluster randomized trial.

OBJECTIVE: The quality of referrals is often criticized, and the effectiveness of improvement efforts remains uncertain. We assessed the impact of a rheumatologist triaging patients in primary care on the appropriateness of referrals to secondary care, healthcare utilization, and patient experience and outcomes. METHOD: A cluster randomized controlled trial was conducted with patients experiencing musculoskeletal complaints. Intervention practices deployed an experienced rheumatologist triaging patients through in-person review. Usual care was performed in control practices, where practitioners referred patients based on their own judgement. The primary outcome was the proportion of inflammatory rheumatic diseases (IRDs) diagnosed by rheumatologists in referred patients. Healthcare utilization (iMTA Medical Consumption Questionnaire), quality of life (EuroQol 5 Dimensions), and experience of care (Consumer Quality Index) were determined after 3 months of follow-up. Data were analysed according to the intention-to-treat principle. RESULTS: In total, 544 participants were included [mean age 51.4 (range 18-87) years; 24% were men]. Of all referred patients, 51% had an IRD in the intervention group versus 21% in the control group (p = 0.035). After 3 months of follow-up, patients from the triage intervention showed lower healthcare utilization (p = 0.006) and higher quality of life (p = 0.011), without a decline in experienced quality of care (p = 0.712), compared to controls. CONCLUSION: Triage by a rheumatologist in primary care provides appropriate care and adequate experience of care, leading to a higher quality of life. Long-term evidence is needed to assess the value on cost-effectiveness before implementing this strategy nationwide.

A systematic review on time trend incidence of rheumatoid arthritis in outpatient rheumatology clinics.

Objectives: To classify patients with rheumatoid arthritis (RA) in an earlier stage of the disease, the ACR/EULAR classification criteria were updated in 2010. These criteria might have led to an increased incidence of RA in the rheumatology clinic. Since a higher incidence increases the socio-economic burden of RA, it is worthwhile to evaluate whether there is a time effect. Materials and methods: A systematic review was conducted using Embase, Medline Ovid, Cochrane Central, and Web of Science from database inception to February 2021. Included were only articles that addressed incidence rates of rheumatoid arthritis from rheumatology outpatient clinics. Results: Of the 6,289 publications only 243 publications on RA were found eligible for full-text review. Nine studies were included reporting incidence. The pooled incidence for RA was 11% (95% CI 6-16%) per year. Over time the incidence increased after the introduction of the 2010 ACR/EULAR classification criteria. Overall there was a high intragroup heterogeneity (I 2 = 97.93%, p < 0.001), caused by geographical area, study design and differences in case definitions. Conclusion: Although the incidence seems to increase after the introduction of the 2010 ACR/EULAR criteria, no conclusions can be drawn on this time effect due to heterogeneity.

T and B Cell Composition and Cytokine Producing Capacity Before and After Bariatric Surgery.

Morbid obesity is associated with a chronic state of low-grade inflammation, which may lead to accelerated differentiation of T and B cells. These differentiated immune cells are strongly cytotoxic and have an increased pro-inflammatory cytokine producing capacity. Furthermore, the anti-inflammatory function of the T and B cells decreases. The aim of this study was to evaluate the effect of morbid obesity on the subset profile and cytokine producing capacity of T and B cells. Subsequently, we assessed whether bariatric surgery affected the subset profile and cytokine producing capacity of these cells. We determined the proportion of T and B cell subsets and their cytokine producing capacity in peripheral blood collected from 23 morbidly obese patients before and three months after bariatric surgery using flow-cytometry. We compared this with the results of 25 lean controls. Both CD4+ and CD8+ T cells showed a more differentiated subset profile in morbidly obese patients as compared to lean controls, which was not recovered three months after bariatric surgery. The B cell composition of morbidly obese patients after bariatric surgery adjusted towards the profile of lean controls. However, the IL-2 and IFN-γ producing capacity of CD8+ T cells and the IL-2, IFN-γ, TNF-α and IL-10 producing capacity of B cells was not restored three months after bariatric surgery. In conclusion, the data suggest that the immune system has the capacity to recover from the detrimental effects of morbid obesity within three months after bariatric surgery in terms of cell composition; however, this was not seen in terms of cytokine producing capacity. The full restoration of the immune system after bariatric surgery may thus take longer.

The impact of a disease flare during tapering of DMARDs on the lives of rheumatoid arthritis patients.

OBJECTIVES: To determine the impact of a disease flare on patient reported outcome measures (PROMs) in rheumatoid arthritis (RA) patients, who are tapering treatment. METHODS: Data were used from the TARA trial; a multicenter, randomized controlled trial in which RA patients, with a well-controlled disease (DAS≤2.4 and SJC≤1) for at least 6 months, gradually tapered their DMARDs. PROMs of patients with a flare (DAS>2.4 and/or SJC>1) were compared every three months before and after a flare with their own norm values. Linear Mixed Models were used to investigate whether a disease flare influenced functional ability (HAQ-DI), fatigue (BRAF-MDQ), quality of life (EQ-5D and SF36), anxiety and depression (HADS), morning stiffness, general health (GH) and worker productivity, and if so, the duration was determined. For unemployment and sick leave we used descriptive statistics. RESULTS: A flare negatively influenced GH, morning stiffness, HAQ-DI, EQ-5D, BRAF-MDQ, and the SF36 physical component scale and this effect lasted >3 months. Except for the HAQ-DI, effect sizes exceeded the minimum clinically important differences (MCIDs). For the physical outcomes effects lasted >6 months. Worker productivity was not significantly affected by a flare. CONCLUSION: A disease flare influenced patients' lives, the largest effect was seen in the physical outcomes, and lasted 6 months. Although on a group level effect sizes for the separate PROMs were not always significant or larger than specific MCIDs, a disease flare can still be of great importance for individual patients.

Fatigue in early, intensively treated and tight-controlled rheumatoid arthritis patients is frequent and persistent: a prospective study.

Fatigue has a large impact on quality of life and is still unmanageable for many patients. Study aims were describe (1) the prevalence and pattern of fatigue over time in patients with early rheumatoid arthritis under a treat-to-target strategy and (2) identify predictive factors for worsening and recovering of fatigue over time. Data from the tREACH study were used, comparing different treatment strategies with fatigue as secondary objective. Patient outcomes on fatigue, quality of life, depression, and coping were obtained every 6 months and clinically assessed every 3 months. Prediction of fatigue at 12 months was investigated with an ROC curve. Analysis was stratified into non-fatigue and fatigue at baseline. Logistic regression was used for the evolution of fatigue in relation with the covariates over time. Almost half of all patients (n = 246) had high fatigue levels at baseline, decreasing slightly over time. At 12 months, 43% of patients were fatigued; while 23% of the initially fatigued patients showed lower levels of fatigue, the fatigue level had increased in 15% of the initially non-fatigued patients. The strongest predictor of fatigue was the previous fatigue levels (AUC 0.89). Higher score on the depression scale and coping with limitations was associated with developing fatigue over time in the initially non-fatigued group. Despite a strict treat-to-target strategy, fatigue remained an overall problem during the first year of treatment, and was mainly predicted by its baseline status. In subgroups, a small additional effect of depression was seen. Monitoring fatigue and depression may be important in managing fatigue.

Effects of psychosocial factors on monitoring treatment effect in newly diagnosed rheumatoid arthritis patients over time: response data from the tREACH study.

OBJECTIVES: To investigate whether, apart from effects of patient- and disease-related factors, psychosocial factors have additional effects on disease activity; and which factors are most influential during the first year of treatment in early rheumatoid arthritis (RA). METHOD: The study assessed 15 month follow-up data from patients in tREACH, a randomized clinical trial comparing initial triple disease-modifying anti-rheumatic drug therapy to methotrexate monotherapy, with glucocorticoid bridging in both groups. Patients were evaluated every 3 months and treated to target. Associations between Disease Activity Score (DAS) at 3, 9, and 15 months and psychosocial factors (anxiety, depression, fatigue, and coping with pain) at the previous visit were assessed by multivariable linear regression correcting for demographic, clinical, and treatment-related factors. RESULTS: At 3, 9, and 15 months of follow-up, 265, 251, and 162 patients, respectively, were available for analysis. Baseline anxiety and coping with pain were associated with DAS at 3 months; coping with pain at 6 months was associated with DAS at 9 months, and fatigue at 12 months with DAS at 15 months. Psychosocial factors were moderately correlated. Effects on DAS were mainly due to tender joint count and global health. CONCLUSION: Psychosocial factors have additional effects on DAS throughout the first year of treatment in early RA. A change was observed from anxiety and coping with pain at baseline being associated with subsequent DAS towards fatigue being associated with subsequent DAS at 12 months. Owing to the explorative nature of this study, more research is needed to confirm this pattern.

Factors affecting the rate of surgical site infection in patients after hemiarthroplasty of the hip following a fracture of the neck of the femur.

AIMS: Surgical site infection can be a devastating complication of hemiarthroplasty of the hip, when performed in elderly patients with a displaced fracture of the femoral neck. It results in a prolonged stay in hospital, a poor outcome and increased costs. Many studies have identified risk and prognostic factors for deep infection. However, most have combined the rates of infection following total hip arthroplasty and internal fixation as well as hemiarthroplasty, despite the fact that they are different entities. The aim of this study was to clarify the risk and prognostic factors causing deep infection after hemiarthroplasty alone. PATIENTS AND METHODS: Data were extracted from a prospective hip fracture database and completed by retrospective review of the hospital records. A total of 916 patients undergoing a hemiarthroplasty in two level II trauma teaching hospitals between 01 January 2011 and 01 May 2016 were included. We analysed the potential peri-operative risk factors with univariable and multivariable logistic regression analysis. RESULTS: A total of 92 patients (10%) had a surgical site infection, and 44 (4.9%) developed a deep infection. After univariable analyses, the multivariable model showed that the level of experience of the surgeon measured by the number of hemiarthroplasties performed per year was a significant prognostic factor (odds ratio (OR) 0.93, p = 0.042) for the development of an infection. Secondly, the development of a haematoma (OR 9.6, p < 0.001), a re-operation (OR 4.7, p = 0.004) and an operating time of < 45 mins (OR 5.1, p = 0.002) or > 90 mins (OR 2.7, p = 0.034) were also significant factors. CONCLUSION: There was a significant association between the experience of the surgeon and the rate of deep infection. Secondly, a haematoma, a re-operation and both shorter and longer operating times were associated with an increased risk of deep infection after hemiarthroplasty. No association was found between deep infection and the anatomical approach, the time when surgery was undertaken and the use of a drain. Cite this article: Bone Joint J 2017;99-B:1088-94.

Tapering conventional synthetic DMARDs in patients with early arthritis in sustained remission: 2-year follow-up of the tREACH trial.

OBJECTIVES: With early and intensive treatment many patients with early RA attain remission. Aims were to investigate (1) the frequency and time to sustained remission and subsequent tapering in patients initially treated with conventional synthetic disease modifying anti-rheumatic drug ((cs)DMARD) strategies and (2) the frequency and time to flare and regained remission in patients tapering csDMARDs and biological (b)DMARDs during 2 years of follow-up. METHODS: Two-year follow-up data from the treatment in the Rotterdam Early Arthritis Cohort (tREACH) cohort were used. Patients were randomised to initial treatment with triple DMARD therapy (iTDT) with glucocorticoid (GC) bridging or methotrexate monotherapy (iMM) with GC bridging. Patients were evaluated every 3 months. In case Disease Activity Score (DAS) was >2.4 treatment was switched to a TNF-blocker. In case DAS<1.6 at 2 consecutive time points, tapering was initiated according to protocol. Outcomes were rates of sustained remission (DAS<1.6 at 2 consecutive time points), flare (medication increase after tapering) and remission after flare (DAS<1.6). Data were analysed using Kaplan-Meier analyses. RESULTS: During 2 years of follow-up, sustained remission was achieved at least once by 159 (57%) of patients, of whom 118 and 23 patients initiated tapering of csDMARDs and bDMARDs, respectively. Thirty-four patients achieved drug-free remission. Flare rates were 41% and 37% and within 1 year, respectively. After flare, 65% of patients tapering csDMARDs re-achieved remission within 6 months after treatment intensification. CONCLUSIONS: Regardless of initial treatment strategy, 57% of patients achieved sustained remission during 2 years of follow-up. Flare rates were 41% and 37% within 12 months in patients tapering csDMARDs and bDMARDs, respectively. TRIAL REGISTRATION NUMBER: ISRCTN26791028; Post-results.