Long-term clinical and radiological effectiveness and safety of ultralow doses of rituximab in rheumatoid arthritis: observational extension of the REDO trial.

BACKGROUND: The REDO trial (REtreatment with Rituximab in RhEmatoid arthritis: Disease Outcome after Dose Optimisation) showed similar disease activity for retreatment with ultralow doses (200 mg and 500 mg per 6 months) compared with standard low-dose rituximab (RTX, 1000 mg per 6 months). We performed an observational extension study of the REDO trial to assess long-term effectiveness. METHODS: Patients from the REDO trial were followed from start of the trial to censoring in April 2021. RTX use was at the discretion of patient and rheumatologist using treat to target. The primary outcome was disease activity (disease activity score in 28 joints C-reactive protein (DAS28-CRP)), analysed using a longitudinal mixed model by original randomisation and time-varying RTX dose. The original DAS28-CRP non-inferiority (NI) margin of 0.6 was used. RTX dose and persistence, safety and radiological outcomes were also assessed. FINDINGS: Data from 126 of 142 REDO patients was collected from 15 December 2016, up to 30 April 2021. Drop-outs continued treatment elsewhere (n=3) or did not consent (n=13).Disease activity did not differ by original randomisation group: 1000 mg mean DAS28-CRP (95% CI) of 2.2 (2.0 to 2.5), 500 mg 2.3 (2.1 to 2.4) and 200 mg 2.4 (2.2 to 2.5). Lower time-varying RTX dose was associated with higher DAS28-CRP (0.22 (95% CI 0.05 to 0.40) higher for 200 mg/6 months compared with 1000 mg/6 months), but remained within the NI-margin. RTX persistence was 93%. Median RTX dose was 978 mg (IQR 684-1413) per year, and no association was found between RTX dose and adverse events or radiological damage. INTERPRETATION: Long-term use of ultralow doses of RTX is effective in patients with rheumatoid arthritis responding to standard dose RTX.

Efficacy of methylprednisolone in very early systemic sclerosis: results of the "Hit hard and early'' randomized controlled trial.

OBJECTIVE: We hypothesized that glucocorticoids would induce remission in very early Systemic Sclerosis patients by inhibition of inflammation driving the disease. We examined the efficacy and safety of methylprednisolone in very early Systemic Sclerosis. METHODS: In this trial adults with puffy fingers for less than three years, specific auto-antibodies and meeting the Very Early Diagnosis of Systemic Sclerosis criteria were randomly assigned (2:1) to methylprednisolone 1000 mg intravenously or placebo for 3 consecutive days 3 times with monthly intervals. The primary end point was nailfold capillary density at week 12. Capillary density at 52 weeks, number of megacapillaries, and patient-reported outcomes were secondary outcomes. In addition, we assessed disease progression and lung function decline over 52 weeks. We used linear regression analyses adjusted for baseline values and stratification variables to estimate differences between groups. RESULTS: Between February 2017 and February 2021, 87 patients were screened, of whom 30 (70% female, median (IQR) age 52·9 (40·8-60·8) years, median (IQR) disease duration 11.4 (4.6-18.6) months) were randomly assigned to methylprednisolone (n = 21) or placebo (n = 9). We found no difference in nailfold capillary density at 12 weeks: -0.5 (95% CI 1.1, 0.2) nor in any of the secondary outcomes. Eleven (37%) patients showed disease progression during 1 year follow up, 7 (23%) patients had a relevant pulmonary function decline. No serious adverse events were reported. CONCLUSIONS: No clinically relevant effect of short-term methylprednisolone in patients with very early Systemic Sclerosis was observed. A substantial proportion of patients showed disease progression.

Impairment in work and activities of daily life in patients with psoriasis: results of the prospective BioCAPTURE registry.

Background: Little is known about the extent of impairments in work and activities of daily life (ADL) in patients with psoriasis, and the influence of contextual factors such as disease-related characteristics and treatment. Therefore, this study aimed to assess these impairments in patients with psoriasis who started using biologicals/small molecule inhibitors.Methods: Using data from the prospective BioCAPTURE registry, we collected patient, disease, and treatment parameters, as well as work/ADL impairments at baseline, 6 and 12 months. Changes in impairment parameters and correlations between impairment and patient/disease characteristics were assessed using generalized estimating equations.Results: We included 194 patients in our analysis. After biological initiation, disease activity decreased significantly (PASI 11.2 at baseline versus 3.9 at 12 months, p < 0.001). Work-for-pay in this cohort was lower than in the Dutch general population (53% versus 67%, p = 0.01). In patients who had work-for-pay, presenteeism improved over time (5% at baseline versus 0% at 12 months, p = 0.04). Up to half of the patients reported impairments in ADL, which did not change over time. Associations between impairments and contextual factors varied, but all impairments were associated with worse mental/physical general functioning.Conclusion: Patients with psoriasis using biologicals are less likely to have work-for-pay. Treatment improves the work productivity of employed patients, but we were unable to detect changes in ADL performance.

Comparing the evidence for botulinum neurotoxin injections in paediatric anterior drooling: a scoping review.

Paediatric anterior drooling has a major impact on the daily lives of children and caregivers. Intraglandular botulinum neurotoxin type-A (BoNT-A) injections are considered an effective treatment to diminish drooling. However, there is no international consensus on which major salivary glands should be injected to obtain optimal treatment effect while minimizing the risk of side effects. This scoping review aimed to explore the evidence for submandibular BoNT-A injections and concurrent submandibular and parotid (i.e. four-gland) injections, respectively, and assess whether outcomes could be compared across studies to improve decision making regarding the optimal initial BoNT-A treatment approach for paediatric anterior drooling. PubMed, Embase, and Web of Science were searched to identify relevant studies (until October 1, 2023) on submandibular or four-gland BoNT-A injections for the treatment of anterior drooling in children with neurodevelopmental disabilities. Similarities and differences in treatment, patient, outcome, and follow-up characteristics were assessed. Twenty-eight papers were identified; 7 reporting on submandibular injections and 21 on four-gland injections. No major differences in treatment procedures or timing of follow-up were found. However, patient characteristics were poorly reported, there was great variety in outcome measurement, and the assessment of side effects was not clearly described.   Conclusion: This review highlights heterogeneity in outcome measures and patient population descriptors among studies on paediatric BoNT-A injections, limiting the ability to compare treatment effectiveness between submandibular and four-gland injections. These findings emphasize the need for more extensive and uniform reporting of patient characteristics and the implementation of a core outcome measurement set to allow for comparison of results between studies and facilitate the optimization of clinical practice guidelines. What is Known: • There is no international consensus on which salivary glands to initially inject with BoNT-A to treat paediatric drooling. What is New: • Concluding on the optimal initial BoNT-A treatment based on literature is currently infeasible. There is considerable heterogeneity in outcome measures used to quantify anterior drooling.and clinical characteristics of children treated with intraglandular BoNT-A are generally insufficiently reported. • Consensus-based sets of outcome measures and patient characteristics should be developed and implemented.

Predicting non-response to intraglandular botulinum neurotoxin A injections for drooling in children with neurodevelopmental disabilities.

AIM: To develop robust multivariable prediction models for non-response to (1) submandibular botulinum neurotoxin A (BoNT-A) injections and (2) concurrent submandibular and parotid (four-gland) injections, to guide treatment decisions for drooling in children with neurodevelopmental disabilities, including cerebral palsy. METHOD: This was a retrospective cohort study including 262 children (155 males/107 females, median age 7 years 11 months [IQR 5 years 1 month], range 4 years 0 months - 17 years 11 months) receiving submandibular injections and 74 children (52 males/22 females, median age 7 years 7 months [IQR 4 years 3 months], range 4 years 9 months - 18 years 8 months) receiving four-gland injections. Multivariable logistic regression analyses were used to estimate associations between candidate predictors and non-response 8 weeks after injection. RESULTS: Ninety-six children (37%) were non-responders to submandibular injections, for which developmental age was the strongest predictor (adjusted odds ratio [aOR] 2.13; 95% confidence interval [CI] 1.02-4.45 for developmental age <4 years or 4-6 years with IQ <70). Other characteristics that showed a trend towards an increased risk of non-response were diagnosis, sex, and head position. Thirty-four children (46%) were non-responders to four-gland injections, for which tongue protrusion (aOR 3.10; 95% CI 1.14-8.43) seemed most predictive, whereas multiple preceding submandibular injections (aOR 0.34; 95% CI 0.10-1.16) showed a trend towards being protective. Predictors were, however, unstable across different definitions of non-response and both models (i.e. submandibular and four-gland) had insufficient discriminative ability. INTERPRETATION: Potential predictors of non-response to BoNT-A injections were identified. Nevertheless, the developed prediction models seemed inadequate for guidance of treatment decisions.

Virtues in Competency-Based Assessment Frameworks: A Text Analysis.

Introduction: Official documentation of specialty training provides comprehensive and elaborate criteria to assess residents. These criteria are commonly described in terms of competency roles and entrustable professional activities (EPA's), but they may also implicitly encompass virtues. Virtues are desirable personal qualities that enable a person, in this case, a medical specialist, to make and act on the right decisions. We articulate these virtues and explore the resulting implied ideal of a medical professional. Method: We applied a two-staged virtue ethical content analysis to analyze documents, specific to the Dutch training program of the Ear, Nose, and Throat (ENT) specialty. First, we identified explicit references to virtues. Next, we articulated implicit virtues through interpretation. The results were categorized into cardinal, intellectual, moral, and professional virtues. Results: Thirty virtues were identified in the ENT- training program. Amongst them, practical wisdom, temperance, and commitment. Furthermore, integrity, curiosity, flexibility, attentiveness, trustworthiness and calmness are often implicitly assumed. Notable findings are the emphasis on efficiency and effectiveness. Together, these virtues depict an ideal of a future medical specialist. Conclusion: Our findings suggest that competency-frameworks and EPA's implicitly appeal to virtues and articulate a specific ideal surgeon. Explicit attention for virtue development and discussion of the role and relevance of implied ideal professionals in terms of virtues could further improve specialty training.

Nailfold capillaroscopy and candidate-biomarker levels in systemic sclerosis-associated pulmonary hypertension: A cross-sectional study.

Objectives: Pulmonary hypertension is one of the leading causes of death in systemic sclerosis. Early detection and treatment of pulmonary hypertension in systemic sclerosis is crucial. Nailfold capillaroscopy microscopy, vascular autoantibodies AT1R and ETAR, and several candidate-biomarkers have the potential to serve as noninvasive tools to identify systemic sclerosis patients at risk for developing pulmonary hypertension. Here, we explore the classifying potential of nailfold capillaroscopy microscopy characteristics and serum levels of selected candidate-biomarkers in a sample of systemic sclerosis patients with and without different forms of pulmonary hypertension. Methods: A total of 81 consecutive systemic sclerosis patients were included, 40 with systemic sclerosis pulmonary hypertension and 41 with no pulmonary hypertension. In each group, quantitative and qualitative nailfold capillaroscopy microscopy characteristics, vascular autoantibodies AT1R and ETAR, and serum levels of 24 soluble serum factors were determined. For evaluation of the nailfold capillaroscopy microscopy characteristics, linear regression analysis accounting for age, sex, and diffusing capacity of the lungs for carbon monoxide percentage predicted was used. Autoantibodies and soluble serum factor levels were compared using two-sample t test with equal variances. Results: No statistically significant differences were observed in quantitative or qualitative nailfold capillaroscopy microscopy characteristics, or vascular autoantibody ETAR and AT1R titer between systemic sclerosis-pulmonary hypertension and systemic sclerosis-no pulmonary hypertension. In contrast, several serum levels of soluble factors differed between groups: Endostatin, sVCAM, and VEGFD were increased, and CXCL4, sVEGFR2, and PDGF-AB/BB were decreased in systemic sclerosis-pulmonary hypertension. Random forest classification identified Endostatin and CXCL4 as the most predictive classifiers to distinguish systemic sclerosispulmonary hypertension from systemic sclerosis-no pulmonary hypertension. Conclusion: This study shows the potential for several soluble serum factors to distinguish systemic sclerosis-pulmonary hypertension from systemic sclerosis-no pulmonary hypertension. We found no classifying potential for qualitative or quantitative nailfold capillaroscopy microscopy characteristics, or vascular autoantibodies.

Prioritizing parotid gland surgery: A call for the implementation of the MSRSGC classification.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is developed to aid diagnosis and management of salivary gland tumors. This study evaluates the time-to-treatment initiation (TTI) for parotid gland tumors in the Netherlands and relates these to the MSRSGC classification. Subsequently, the use of the MSRSGC in the Netherlands is evaluated. METHODS: Data regarding fine-needle aspiration cytology (FNAC) and histopathological resections of the parotid were gathered from the Dutch nationwide pathology data bank (PALGA). The TTI was calculated for each MSRSGC category and type of treating center. FNACs performed from 2018 to 2021 were gathered from PALGA to estimate how frequently the MSRSGC classification was applied. RESULTS: Median TTI in days were 86 for nondiagnostic (MSRSGC I), 75 for nonneoplastic (MSRSGC II), 65 for atypia of unknown significance (AUS) (MSRSGC III), 89 for benign (MSRSGC IVa), 52 for salivary gland neoplasm of unknown malignant potential (SUMP) (MSRSGC IVb), 31 for suspected malignant (MSRSGC V), and 30 for malignant (MSRSGC VI) categories. Significant variation in the TTI between the types of treating centers was found for the nondiagnostic, nonneoplastic, AUS, SUMP, and suspected malignant categories. In the first 3 years after the introduction of the MSRSGC, the pathologist stated the MSRSGC classification in 6.4% of all reports. CONCLUSIONS: The median TTI for most categories is long, and there is significant interhospital variation in TTI. Preoperative risk stratification and treatment prioritization in parotid gland surgery in the Netherlands should be improved. The MSRSGC could contribute to this. Until 2021, the MSRSGS classification was implemented on a limited scale in the Netherlands.

Non-Medical Switching from Tocilizumab to Sarilumab in Rheumatoid Arthritis Patients with Low Disease Activity, an Observational Study.

Tocilizumab and sarilumab are IL-6-receptor antagonists registered for rheumatoid arthritis (RA), with equal effectiveness and safety. Switching from tocilizumab to sarilumab could be a strategy to reduce injection burden, in case of drug shortages, and to reduce costs. This study therefore aims to investigate the effectiveness and safety of switching patients with RA with well-controlled disease under tocilizumab treatment to sarilumab. Patients with RA with low Disease Activity Score 28 (DAS28;-CRP < 2.9 or < 3.5 with clinical judgment), on stable dose tocilizumab (> 6 months) were offered to switch to sarilumab. Patients who switched and consented were followed for 6 months. Sarilumab was started at 200 mg and double the last tocilizumab interval. Co-primary outcomes at 6 months were (i) the 90% confidence interval (CI) of DAS28-CRP change from baseline compared with the non-inferiority margin of 0.6 and (ii) the 90% CI of the proportion of patients persisting with sarilumab, compared with a prespecified minimum of 70%. Of 50 invited patients, 25 agreed to switch to sarilumab, and 23 patients switched and were included. One patient was lost to follow-up immediately after inclusion, therefore 22 patients are included in the analyses. At 6 months, mean change in DAS28-CRP was 0.48 (90% CI: 0.11-0.87), compared with the non-inferiority margin of 0.6. Sarilumab persistence was 68% (90% CI: 51-82%, 15 out of 22 patients), compared with the prespecified minimum of 70%. Non-medical switching from tocilizumab to sarilumab in patients doing well on tocilizumab failed to show non-inferiority regarding disease activity and drug persistence.

Development of a New Referral Tool to Identify Psoriasis Patients with Concomitant Psoriatic Arthritis: Results of the Prospective DAPPER Cohort.

Patients with psoriasis are at risk of developing psoriatic arthritis, which can lead to joint damage. While screening questionnaires have been developed, their performance varies. The objective of this study was to develop a referral tool for dermatologists to identify psoriasis patients with concomitant psoriatic arthritis for rheumatological referral. This study used data from the DAPPER study, in which psoriasis patients were screened by a rheumatologist for the presence of concomitant psoriatic arthritis. Multivariable regression analysis was used to identify predictive variables for the presence of concomitant psoriatic arthritis: treatment history with conventional systemic drugs (odds ratio (OR) 2.97, 95% confidence interval (95% CI) 1.01-8.74, p = 0.04), treatment history with biologicals/small molecule inhibitors (OR 2.90, 95% CI 1.52-5.53, p = 0.01), patient-reported history of joint pain not caused by trauma (OR 4.23, 95% CI 1.21-14.79, p = 0.01), patient-reported history of swollen joints (OR 4.25, 95% CI 2.17-8.32, p < 0.001), and patient-reported history of sausage-like swollen digits (OR 2.38, 95% CI 1.25-4.55, p = 0.01). Based on these variables, a referral tool was created with an area under the curve of 0.82. This referral tool could be used to aid dermatologists to identify psoriasis patients with concomitant psoriatic arthritis, who may benefit from rheumatological referral.

Postoperative Airway Management after Submandibular Duct Relocation in 96 Drooling Children and Adolescents.

The aim of this study was to evaluate our institutions airway management and complications after submandibular duct relocation (SMDR). We analysed a historic cohort of children and adolescents who were examined at the Multidisciplinary Saliva Control Centre between March 2005 and April 2016. Ninety-six patients underwent SMDR for excessive drooling. We studied details of the surgical procedure, postoperative swelling and other complications. Ninety-six patients, 62 males and 34 females, were treated consecutively by SMDR. Mean age at time of surgery was 14 years and 11 months. The ASA physical status was 2 in most patients. The majority of children were diagnosed with cerebral palsy (67.7%). Postoperative swelling of the floor of the mouth or tongue was reported in 31 patients (32.3%). The swelling was mild and transient in 22 patients (22.9%) but profound swelling was seen in nine patients (9.4%). In 4.2% of the patients the airway was compromised. In general, SMDR is a well-tolerated procedure, but we should be aware of swelling of the tongue and floor of the mouth. This may lead to a prolonged period of endotracheal intubation or a need for reintubation which can be challenging. After extensive intra-oral surgery such as SMDR we strongly recommend a extended perioperative intubation and extubation after the airway is checked and secure.

Long-term effects of submandibular gland excision on drooling in children with neurodevelopmental disorders: A cross-sectional study.

AIM: Submandibular gland excision (SMGE) is suitable for the management of drooling in patients with non-progressive neurodisabilities. We aimed to investigate the long-term effects of SMGE. METHOD: Patients who had SMGE between 2007 and 2018 were included. Main outcomes were a Visual Analogue Scale (VAS), Drooling Severity (DS), and Drooling Frequency (DF) collected at baseline, 8 weeks, 32 weeks and with a median of 313 weeks after SMGE (long-term). Secondary outcomes were satisfaction with the procedure, Drooling Quotient (DQ) and adverse events (AEs). RESULTS: We included thirty-five patients in the long-term analysis with a mean age of 14.5 years. A baseline VAS score of 80.4 was found, which improved on the long-term (mean difference -21.8, t(26) = 4.636, p < 0.0005)). DS and DF decreased significantly at the long-term compared to baseline (Z = -4.361, p < 0.0001 for DS, Z = -3.065, p = 0.002 for DF). Twenty-three out of 35 (66%) patients would recommend the procedure to peers. INTERPRETATION: This study indicates a long-term stable effect on drooling after SMGE in patients with anterior drooling. Recurrence of drooling occurs due to unknown reasons, nevertheless most caregivers and/or patients are still satisfied and would recommend the procedure to others.

Outpatient parotidectomy with or without the use of a post-operative drain: A retrospective bi-institutional study.

OBJECTIVE: Parotid surgery is historically performed as an inpatient procedure and suctions drains are predominantly used during surgery. Recent literature provides evidence that outpatient parotid surgery is safe and effective. Our study aims to describe the results of drainless outpatient parotidectomy and outpatient parotidectomy with drain placement and compare their outcomes. DESIGN: Retrospective cohort study. SETTING: Bi-institutional retrospective cohort study. PARTICIPANTS: Patients that underwent outpatient drain-less parotidectomy and patients that underwent outpatient parotidectomy with post-operative drain placement. MAIN OUTCOME MEASURES: Complication rates, unplanned post-operative visits, unplanned prolonged stay. RESULTS: Three hundred eighty patients underwent outpatient parotidectomy with drain placement and 31 patients underwent outpatient drainless parotidectomy in two different hospitals. The incidence of haematoma (drain: 3.1% vs. drainless: 0%, p = 1), infection (drain: 14.3% vs. drainless: 13.8%, p = 1) and salivary fistula (drain: 5.6% vs. drainless: 3.4, p = 1) were comparable between both groups. Seroma or sialocele was more frequently seen in the drain-less group (27.6% vs. 6.2%, p < .001), but were all managed conservatively. Within 10 days after surgery, unplanned visits seemed more frequent in the drain group, although the difference was not statistically significant (14.9% vs. 3.4%, p = .16). CONCLUSIONS: Outpatient parotid surgery with or without the use of a post-operative drain is safe, practical and feasible. Same-day discharge with and without drain placement yield comparable outcomes. However, the results need to be interpreted cautiously as this study was limited by a small cohort of parotidectomies without drain placement. Future studies should further compare both approaches.

(Dis)agreement of polymyalgia rheumatica relapse criteria, and prediction of relapse in a retrospective cohort.

BACKGROUND: To develop and assess a prediction model for polymyalgia rheumatica (PMR) relapse within the first year of glucocorticoid (GC) treatment. METHODS: A retrospective PMR cohort (clinical diagnosis) from a rheumatology department was used. All visits > 30 days after starting GC treatment and with > 2.5 mg/day oral prednisolone were used as potential relapse visits. Often used relapse criteria (1) rheumatologist judgement, (2) treatment intensification-based relapse) were assessed for agreement in this cohort. The proportion of patients with treatment-based relapse within 1 and 2 years of treatment and the relapse incidence rate were used to assess unadjusted associations with candidate predictors using logistic and Poisson regression respectively. After using a multiple imputation method, a multivariable model was developed and assessed to predict the occurrence (yes/no) of relapse within the first year of treatment. RESULTS: Data from 417 patients was used. Relapse occurred at 399 and 321 (of 2422) visits based on the rheumatologist judgement- and treatment-based criteria respectively, with low to moderate agreement between the two (87% (95% CI 0.86-0.88), with κ = 0.49 (95% CI 0.44-0.54)). Treatment-based relapse within the first two years was significantly associated with CRP, ESR, and pre-treatment symptom duration, and incidence rate with only CRP and ESR. A model to predict treatment intensification within the first year of treatment was developed using sex, medical history of cardiovascular disease and malignancies, pre-treatment symptom duration, ESR, and Hb, with an AUC of 0.60-0.65. CONCLUSION: PMR relapse occurs frequently, although commonly used criteria only show moderate agreement, underlining the importance of a uniform definition and criteria of a PMR specific relapse. A model to predict treatment intensification was developed using practical predictors, although its performance was modest.

Discovery of Psoriatic Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER) Study: A Prospective Observational Cohort.

Patients with psoriasis are at risk of developing psoriatic arthritis, which can lead to irreversible joint damage. However, a proportion of patients with psoriasis and concomitant psoriatic arthritis remain undiscovered in practice. The aims of this study were: to prospectively determine prevalence, characteristics, and disease burden of psoriatic arthritis in a psoriasis population; and to determine the prevalence and characteristics of patients with active psoriatic arthritis, who were not under rheumatological care. Patients with psoriasis were screened by a rheumatologist at the dermatology outpatient clinic for psoriatic arthritis. Patients with suspected active psoriatic arthritis who were not seeing a rheumatologist were referred to a rheumatologist for confirmation. The total prevalence of psoriatic arthritis in this observational, prospective cohort (n = 303) was 24%. Patients with psoriasis with concomitant psoriatic arthritis had longer duration of skin disease and more often a treatment history with systemic therapies. In this academic, specialized, setting, 2.3% of patients (n = 7), were not receiving rheumatological care despite having active psoriatic arthritis. These patients were characterized by a combination of low (perceived) disease burden and low yield of screening questionnaires, making it difficult for dermatologists to discover psoriatic arthritis in these patients. Thus, screening for more subtle active arthritis in patients with psoriasis in a dermatology setting could be improved.

Treat-to-target dose reduction and withdrawal strategy of TNF inhibitors in psoriatic arthritis and axial spondyloarthritis: a randomised controlled non-inferiority trial.

OBJECTIVES: Tumour necrosis factor inhibitors (TNFi) are effective in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), but are associated with a small (0.6%) increase in serious infection risk, patient burden due to need for self-injection and high costs. Treat-to-target (T2T) tapering might ameliorate these drawbacks, but high-quality evidence on T2T tapering strategies is lacking in PsA and axSpA. METHODS: We performed a pragmatic open-label, monocentre, randomised controlled non-inferiority (NI) trial on T2T tapering of TNFi. Patients with PsA and axSpA using a TNFi with ≥6 months stable low disease activity (LDA) were included. Patients were randomised 2:1 to disease activity-guided T2T with or without tapering until withdrawal and followed-up to 12 months. Primary endpoint was the difference in proportion of patients having LDA at 12 months between groups, compared with a prespecified NI margin of 20%, estimated using a Bayesian prior. RESULTS: 122 patients (64 PsA and 58 axSpA) were randomised to a T2T strategy with (N=81) or without tapering (N=41). The proportion of patients in LDA at 12 months was 69% for the tapering and 73% for the no-tapering group: adjusted difference 5% (Bayesian 95% credible interval: -10% to 19%) which confirms NI considering the NI margin of 20%. The mean percentage of daily defined dose was 53% for the tapering and 91% for the no-tapering group at month 12. CONCLUSIONS: A T2T TNFi strategy with tapering attempt is non-inferior to a T2T strategy without tapering with regard to the proportion of patients still in LDA at 12 months, and results in a substantial reduction of TNFi use. TRIAL REGISTRATION NUMBER: NL 6771.

Economic Evaluation of the Dr. Bart Application in Individuals With Knee and/or Hip Osteoarthritis.

OBJECTIVE: To evaluate the cost-utility and cost-effectiveness of the dr. Bart app compared to usual care in people with osteoarthritis (OA) of the knees and hips, applying a health care payer perspective. METHODS: This economic evaluation was conducted alongside a 6-month randomized controlled trial that included 427 participants. The dr. Bart app is a stand-alone eHealth application that invites users to select pre-formulated goals (i.e., "tiny habits") and triggers for a healthier lifestyle. Self-reported outcome measures were health care costs, quality-adjusted life years (QALYs) according to the EuroQol 5-dimension 3-level (EQ-5D-3L) descriptive system, the EuroQol visual analog scale (QALY VAS), patient activation measure 13 (PAM-13), and 5 subscales of the Knee Injury and Osteoarthritis Outcome Score/Hip Disability and Osteoarthritis Outcome Score. Missing data were multiply imputed, and bootstrapping was used to estimate statistical uncertainty. RESULTS: The mean ± SD age of the study participants was 62.1 ± 7.3 years, and the majority of participants were female (72%). Health care costs were lower in the intervention group compared to the group who received usual care (€-22 [95% confidence interval €-36, -3]). For QALY and QALY VAS, the probability of the dr. Bart app being cost-effective compared to usual care was 0.71 and 0.67, respectively, at a willingness-to-pay (WTP) of €10,000 and 0.64 and 0.56, respectively, at a WTP of €80.000. For self-management behavior, symptoms, pain, and activities of daily living, the probability that the dr. Bart app was cost-effective was >0.82, and the probability that the dr. Bart app was cost-effective in the areas of activities and quality of life was <0.40, regardless of WTP thresholds. CONCLUSION: This economic evaluation showed that costs were lower for the dr. Bart app group compared to the group who received usual care. Given the noninvasive nature of the intervention and the moderate probability of it being cost-effective for the majority of outcomes, the dr. Bart app has the potential to serve as a tool to provide education and goal setting in OA and its treatment options.

Evidence and consensus-based recommendations for non-pharmacological treatment of fatigue, hand function loss, Raynaud's phenomenon and digital ulcers in patients with systemic sclerosis.

OBJECTIVE: SSc is a complex CTD affecting mental and physical health. Fatigue, hand function loss, and RP are the most prevalent disease-specific symptoms of systemic sclerosis. This study aimed to develop consensus and evidence-based recommendations for non-pharmacological treatment of these symptoms. METHODS: A multidisciplinary task force was installed comprising 20 Dutch experts. After agreeing on the method for formulating the recommendations, clinically relevant questions about patient education and treatments were inventoried. During a face-to-face task force meeting, draft recommendations were generated through a systematically structured discussion, following the nominal group technique. To support the recommendations, an extensive literature search was conducted in MEDLINE and six other databases until September 2020, and 20 key systematic reviews, randomized controlled trials, and published recommendations were selected. Moreover, 13 Dutch medical specialists were consulted on non-pharmacological advice regarding RP and digital ulcers. For each recommendation, the level of evidence and the level of agreement was determined. RESULTS: Forty-one evidence and consensus-based recommendations were developed, and 34, concerning treatments and patient education of fatigue, hand function loss, and RP/digital ulcers-related problems, were approved by the task force. CONCLUSIONS: These 34 recommendations provide guidance on non-pharmacological treatment of three of the most frequently described symptoms in patients with systemic sclerosis. The proposed recommendations can guide referrals to health professionals, inform the content of non-pharmacological interventions, and can be used in the development of national and international postgraduate educational offerings.

Flexible Endoscopic Biopsy: Identifying Factors to Increase Accuracy in Diagnosing Benign and Malignant Laryngopharyngeal Pathology.

OBJECTIVES: To assess the influence that several factors, such as the amount of obtained biopsies, difficult procedures, biopsy site and the experience of the attending physician, have on accuracy of flexible endoscopic biopsy (FEB). MATERIALS AND METHODS: 203 FEB procedures for benign or malignant laryngopharyngeal lesions were prospectively included. During the procedure, three representative biopsies (macroscopically containing vital tumor tissue and not only necrosis or healthy tissue) were obtained. The accuracy of each biopsy was separately analyzed. Difficulties during the procedures leading to failure of acquiring three representative biopsies were recorded and classified into tumor, patient and procedural factors. Histological results of FEB were defined correct when consistent with clinical context, additional biopsies or Positron emission tomography-computed tomography (PET-CT) revealed equivalent pathology, or the lesion was stable or resolved in >6 months follow-up. RESULTS: The first representative biopsy yielded a correct diagnosis in 65% of the cases. After the second representative biopsy, 78% was correctly diagnosed. The contribution of the third and fourth representative biopsies to accuracy was 3%. The overall accuracy of FEB was 85%. Difficult procedures were more likely to result in misdiagnosis, whereas biopsy site or experience of the attending physician did not influence results. CONCLUSIONS: FEB was accurate in diagnosing laryngopharyngeal lesions when at least two representative biopsies were obtained. Accuracy of FEB could be further improved by limiting possible constraints during the procedures, for example by selecting, informing, and anesthetizing patients carefully.