Effectiveness of longstanding exercise therapy compared with usual care for people with rheumatoid arthritis and severe functional limitations: a randomised controlled trial.

OBJECTIVES: To compare the effectiveness of longstanding (>52 weeks), supervised exercise therapy with usual care in adults with rheumatoid arthritis (RA) and severe functional limitations. METHODS: Participants were randomised 1:1 to the intervention (individualised goal-setting, active exercises, education and self-management regarding physical activity) or usual care. Primary endpoint was the change in the Patient-Specific Complaints activity ranked 1 (PSC1, 0-10) at 52 weeks. Secondary endpoints included the PSC activities ranked 2 and 3 (PSC2, PSC3), Health Assessment Questionnaire-Disability Index (HAQ-DI), Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL), 6-minute walk test (6MWT), Patient Reported Outcome Measurement Information System Physical Function-10 (PROMIS PF-10) and the Short Form-36 Physical and Mental Component Summary Scales (SF-36 PCS and MCS). (Serious) Adverse events (AEs) were recorded. Measurements were done by blinded assessors. Analyses at 52 weeks were based on the intention-to-treat principle. RESULTS: In total, 217 people (90% female, age 58.8 (SD 12.9) years) were randomised (n=104 intervention, n=98 usual care available for analyses). At 52 weeks, the improvement of the PSC1 was significantly larger in the intervention group (mean difference (95% CI) -1.7 (-2.4, -1.0)). Except for the SF-36 MCS, all secondary outcomes showed significantly greater improvements favouring the intervention (PSC2 -1.8 (-2.4, -1.1), PSC3 -1.7 (-2.4, -1.0), PROMIS PF-10 +3.09 (1.80, 4.38), HAQ-DI -0.17 (-0.29, -0.06), RAQoL -2.03 (-3.39, -0.69), SF-36 PCS +3.83 (1.49, 6.17) and 6MWT +56 (38, 75) m). One mild, transient AE occurred in the intervention group. CONCLUSION: Longstanding, supervised exercise therapy was more effective than usual care in people with RA and severe functional limitations. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL8235), included in the International Clinical Trial Registry Platform (https://trialsearch.who.int/Trial2.aspx?TrialID=NL8235).

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.

One-year effectiveness of long-term exercise therapy in people with axial spondyloarthritis and severe functional limitations.

OBJECTIVE: To evaluate the effectiveness of long-term, personalized, supervised exercise therapy on functional ability compared with usual care in people with axial spondyloarthritis (axSpA) and severe functional limitations. METHODS: Participants were randomly 1:1 assigned to the intervention(maximal 64 sessions, with 14 additional optional sessions of supervised active exercise therapy(e.g. aerobic and muscle strengthening) with individualized goal-setting, education and self-management regarding physical activity) or usual care(care determined by clinician(s) and participants themselves). Primary end point was the change in the Patient-Specific Complaints activity ranked 1 (PSC1 (0-10)) at 52 weeks. Secondary endpoints were the PSC activities ranked 2 and 3, the Bath Ankylosing Spondylitis Functional Index, 6-min walk test, Patient Reported Outcome Measurement Information System-Physical Function-10 and the Short Form-36 Physical and Mental Component Summary Score (SF-36 PCS and MCS). Statistical comparisons comprised independent student t-tests and linear mixed models, based on intention-to-treat. RESULTS: 214 participants(49% female, age 52 (SD 12) years), were randomized to the intervention (n = 110) or usual care (N = 104) group. In the intervention group 93% started treatment, using on average 40.5 sessions (SD 15.1). At 52 weeks, the difference in change in PSC1 between groups favored the intervention group (mean difference [95% CI]; -1.8 [-2.4 to -1.2]). additionally, all secondary outcomes, except the SF-36 MSC, showed significantly greater improvements in the intervention group with effect sizes ranging from 0.4-0.7. CONCLUSION: Long-term, supervised exercise therapy proved more effective than usual care in improving functional disability and physical quality of life in people with axSpA and severe functional limitations. CLINICAL TRIAL REGISTER NUMBER: Netherlands Trial Register NL8238, included in the International Clinical Trial Registry Platform (ICTRP) (https://trialsearch.who.int/Trial2.aspx?TrialID=NL8238).

Quality of reporting and nature of harms in clinical trials on supervised exercise in patients with rheumatoid arthritis or axial spondyloarthritis.

To describe the quality of reporting and the nature of reported harms in clinical studies on the effectiveness of supervised exercises in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA). We performed a systematic review, searching eight databases up to February 2023. Randomized controlled trials (RCTs) evaluating supervised exercises in adults with RA or axSpA were considered eligible. Data on harms were extracted according to the CONSORT Harms 2022 Checklist. Among others, it was recorded if harms were prespecified or non-prespecified. Moreover, the nature of reported harms was listed. Forty RCTs were included for RA and 25 for axSpA, of which 29 (73%) and 13 (52%) reported information on harms. In 13 (33%) RCTs in RA and four (16%) in axSpA, the collection of harms outcomes was described in the methods section. Prespecified outcomes were reported by eight (RA) and two (axSpA) RCTs. Non-specified harms outcomes were reported by six (RA) and four (axSpA) RCTs. Prespecified harms outcomes included measures of pain, disease activity, inflammation, and structural joint changes. The nature of non-prespecified harms outcomes varied largely, with pain being most common. A considerable proportion of trials on supervised exercise in RA or axSpA does not or inadequately report harms outcomes. Pain was the most commonly reported prespecified or non-specified harm. For a considerate interpretation of the balance between benefits and harms of supervised exercise in RA or axSpA, use of the CONSORT Harms 2022 Checklist for the design, conduct and reporting of trials is advocated.

Functional limitations of people with rheumatoid arthritis or axial spondyloarthritis and severe functional disability: a cross-sectional descriptive study.

The objective of the study is to describe the nature of functional limitations in activities and participation in people with Rheumatoid Arthritis (RA) or axial SpondyloArthritis (axSpA) with severe functional disability. Baseline data from people with RA (n = 206) or axSpA (n = 155) and severe functional disability participating in an exercise trial were used. Their three most limited activities were derived from the Patient Specific Complaint (PSC) instrument and linked to the International Classification of Functioning and Health (ICF). The frequencies of ICF categories were calculated and compared with Activities and Participation items of the ICF Core Sets for RA (32 second-level categories) and Ankylosing Spondylitis (AS) (24 second-level categories). In total 618 and 465 PSC activities were linked to 909 (72 unique in total; 25 unique second-level) and 759 (57 unique in total; 23 unique second-level) ICF categories in RA and axSpA. Taking into account all three prioritized activities, the five most frequent limited activities concerned the ICF chapter "Mobility", and included "Walking" (RA and axSpA 2 categories), "Changing basic body position" (RA and axSpA 1 category), "Stair climbing"(RA) and "Grasping" (RA),"Lifting" (axSpA) and "Maintaining a standing position" (axSpA). In RA, 21/32 (66%) and in axSpA 14/24 (58%) unique second-level categories identified in the prioritized activities are present in the Comprehensive Core Sets. Most limitations of people with RA or axSpA and severe functional disability were seen in the ICF chapter "Mobility". Most of the identified ICF categories were covered by the corresponding items of the ICF RA and AS Core Sets.

Association of Low-Dose Colchicine With Incidence of Knee and Hip Replacements : Exploratory Analyses From a Randomized, Controlled, Double-Blind Trial.

BACKGROUND: Osteoarthritis is a major contributor to pain and disability worldwide. Given that inflammation plays an important role in the development of osteoarthritis, anti-inflammatory drugs may slow disease progression. OBJECTIVE: To examine whether colchicine, 0.5 mg daily, reduces incident total knee replacements (TKRs) and total hip replacements (THRs). DESIGN: Exploratory analysis of the LoDoCo2 (Low-Dose Colchicine 2) randomized, controlled, double-blind trial. (Australian New Zealand Clinical Trials Registry: ACTRN12614000093684). SETTING: 43 centers in Australia and the Netherlands. PATIENTS: 5522 patients with chronic coronary artery disease. INTERVENTION: Colchicine, 0.5 mg, or placebo once daily. MEASUREMENTS: The primary outcome was time to first TKR or THR since randomization. All analyses were performed on an intention-to-treat basis. RESULTS: A total of 2762 patients received colchicine and 2760 received placebo during a median follow-up of 28.6 months. During the trial, TKR or THR was performed in 68 patients (2.5%) in the colchicine group and 97 (3.5%) in the placebo group (incidence rate, 0.90 vs. 1.30 per 100 person-years; incidence rate difference, -0.40 [95% CI, -0.74 to -0.06] per 100 person-years; hazard ratio, 0.69 [CI, 0.51 to 0.95]). In sensitivity analyses, similar results were obtained when patients with gout at baseline were excluded and when joint replacements that occurred in the first 3 and 6 months of follow-up were omitted. LIMITATION: LoDoCo2 was not designed to investigate the effect of colchicine in osteoarthritis of the knee or hip and did not collect information specifically on osteoarthritis. CONCLUSION: In this exploratory analysis of the LoDoCo2 trial, use of colchicine, 0.5 mg daily, was associated with a lower incidence of TKR and THR. Further investigation of colchicine therapy to slow disease progression in osteoarthritis is warranted. PRIMARY FUNDING SOURCE: None.

Prioritization of Adverse Consequences After Total Knee Arthroplasty Contributing to a Poor Response: A Best-Worst Scaling Exercise Among Total Knee Arthroplasty Patients and Knee Specialists.

BACKGROUND: Total knee arthroplasty (TKA) can have a number of adverse consequences for patients that might contribute to a poor outcome. This study aimed to prioritize these consequences, from the perspective of patients and knee specialists. METHODS: There were 95 TKA patients and 63 knee specialists who prioritized a set of 29 adverse consequences, based on a previous qualitative study, using a Maximum Difference Scaling method. A hierarchical Bayesian analysis was used to calculate relative importance scores. Differences and agreements between patients versus knee specialists and satisfied versus dissatisfied patients were analyzed using Mann-Whitney-U tests and Kendall's coefficients of concordance. RESULTS: There were 4 out of 5 items in the top-5 of both patients and knee specialists that were similar, however, the ranking was different. The highest-ranked consequence for patients was: "Inability to do normal activities such as walking, cycling, swimming and heavy household chores", while knee specialists ranked: "No improvement in pain during the day" as the highest. "No improvement in walking" was in the patients' top-5, but was not ranked in the top-5 of knee specialists. For satisfied and dissatisfied patients, the top-5 of consequences was similar. CONCLUSION: Comparable perspectives were found for patients versus knee specialists and satisfied versus dissatisfied patients on the importance of adverse consequences after TKA. However, when looking in more detail, differences in ranking of specific subitems suggest that patients place slightly more importance on the inability to perform valued activities, while knee specialists prioritize lack of pain relief to a higher degree.

Inadequate Classification of Poor Response After Total Knee Arthroplasty: A Comparative Analysis of 15 Definitions Using Data From the Dutch Arthroplasty Register and the Osteoarthritis Initiative Database.

BACKGROUND: Variations in defining poor response to total knee arthroplasty (TKA) impede comparisons of response after TKA over time and across hospitals. This study aimed to compare the prevalence, overlap, and discriminative accuracy of 15 definitions of poor response after TKA using 2 databases. METHODS: Data of patients one year after primary TKA from the Dutch Arthroplasty Register (n = 12,275) and the Osteoarthritis Initiative database (n = 204) were used to examine the prevalence, overlap (estimated by Cohen's kappa), and discriminative accuracy (sensitivity, specificity, positive predictive value, negative predictive value, and Youden index) of 15 different definitions of poor response after TKA. In the absence of a gold standard for measuring poor response to TKA, the numeric rating scale satisfaction (≤ 6 'poor responder') and the global assessment of knee impact (dichotomized: ≥ 4 'poor responder') were used as anchors for assessing discriminative accuracy for the Dutch Arthroplasty Register and Osteoarthritis Initiative dataset, respectively. These anchors were chosen based on a prior qualitative study that identified (dis)satisfaction as a central theme of poor responses to TKA by patients and knee specialists. RESULTS: The median (25th to 75th percentile) prevalence of poor responders in the examined definitions was 18.5% (14.0 to 25.5%), and the median Cohen's kappa for the overlap between pairs of definitions was 0.41 (0.32 to 0.59). Median (25th to 75th percentile) sensitivity was 0.45 (0.39 to 0.54), specificity was 0.86 (0.82 to 0.94), positive predictive value was 0.45 (0.34 to 0.62), negative predictive value was 0.89 (0.87 to 0.89), and the Youden index was 0.36 (0.20 to 0.43). CONCLUSIONS: This study found a lack of overlap between different definitions of poor response to TKA. None of the examined definitions adequately classified poor responders to TKA. In contrast, the absence of a poor response could be classified with confidence.

EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis.

OBJECTIVE: To develop evidence-based recommendations for the non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). METHODS: A task force comprising 7 rheumatologists, 15 other healthcare professionals and 3 patients was established. Following a systematic literature review performed to inform the recommendations, statements were formulated, discussed during online meetings and graded based on risk of bias assessment, level of evidence (LoE) and strength of recommendation (SoR; scale A-D, A comprising consistent LoE 1 studies, D comprising LoE 4 or inconsistent studies), following the European Alliance of Associations for Rheumatology standard operating procedure. Level of agreement (LoA; scale 0-10, 0 denoting complete disagreement, 10 denoting complete agreement) was determined for each statement through online voting. RESULTS: Four overarching principles and 12 recommendations were developed. These concerned common and disease-specific aspects of non-pharmacological management. SoR ranged from A to D. The mean LoA with the overarching principles and recommendations ranged from 8.4 to 9.7. Briefly, non-pharmacological management of SLE and SSc should be tailored, person-centred and participatory. It is not intended to preclude but rather complement pharmacotherapy. Patients should be offered education and support for physical exercise, smoking cessation and avoidance of cold exposure. Photoprotection and psychosocial interventions are important for SLE patients, while mouth and hand exercises are important in SSc. CONCLUSIONS: The recommendations will guide healthcare professionals and patients towards a holistic and personalised management of SLE and SSc. Research and educational agendas were developed to address needs towards a higher evidence level, enhancement of clinician-patient communication and improved outcomes.

18F-FDG PET-CT in rheumatoid arthritis patients tapering TNFi: reliability, validity and predictive value.

OBJECTIVES: To investigate the reliability and validity of fluorine-18 fluorodeoxyglucose (18F-FDG) PET-CT scanning (FDG-PET) in RA patients with low disease activity tapering TNF inhibitors (TNFis) and its predictive value for successful tapering or discontinuation. METHODS: Patients in the tapering arm of the Dose REduction Strategies of Subcutaneous TNFi study, a randomized controlled trial of TNFi tapering in RA, underwent FDG-PET before tapering (baseline) and after maximal tapering. A total of 48 joints per scan were scored both visually [FDG-avid joint (FAJ), yes/no] and quantitatively [maximal and mean standardized uptake values (SUVmax and SUVmean)]. Interobserver agreement was calculated in 10 patients at baseline. Quantitative and visual FDG-PET scores were investigated for (multilevel) association with clinical parameters both on a joint and patient level and for the predictive value at baseline and the change between baseline and maximal tapering (Δ) for successful tapering and discontinuation at 18 months. RESULTS: A total of 79 patients underwent FDG-PET. For performance of identification of FAJs on PET, Cohen's κ was 0.49 (range 0.35-0.63). For SUVmax and SUVmean, intraclass correlation coefficients were 0.80 (range 0.77-0.83) and 0.96 (0.9-1.0), respectively. On a joint level, swelling was significantly associated with SUVmax and SUVmean [B coefficients 1.0 (95% CI 0.73, 1.35) and 0.2 (0.08, 0.32), respectively]. On a patient level, only correlation with acute phase reactants was found. FDG-PET scores were not predictive of successful tapering or discontinuation. CONCLUSIONS: Quantitative FDG-PET arthritis scoring in RA patients with low disease activity is reliable and has some construct validity. However, no predictive values were found for FDG-PET parameters for successful tapering and/or discontinuation of TNFi.

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.

Association between healthcare practitioners' beliefs about statins and patients' beliefs and adherence.

AIMS: Adherence to statins ranges from 32% to 79%. Patients' beliefs about medication are associated with adherence. There is lack of insight into the possible association between beliefs of healthcare practitioners (HCPs) about statins and patients' beliefs and adherence. This study aims to examine whether HCPs' beliefs about statins are associated with patients' beliefs and adherence about/to statins. METHODS: Cross-sectional study in 48 pharmacies and affiliated physicians' practices between 3 September 2014 and 20 March 2015. HCPs' (prescribers and pharmacy staff) and patients' beliefs about statins were assessed with the Beliefs about Medicine Questionnaire (BMQ) specific. Adherence to statins was assessed with the MARS-5 questionnaire. Multilevel regression analysis was performed to assess the association between HCPs' beliefs and patients' beliefs and adherence. RESULTS: 1504 patients (mean age 66.8 [s.d. ± 9.9] years, 46.5% female) and 734 HCPs (209 physicians, 118 pharmacists and 366 pharmacy technicians) participated in this study. Patients have higher BMQ necessity (16.9 [s.d. ± 4.3]) and BMQ concern (12.3 [s.d. ± 3.9]) scores than HCPs (15.0 [s.d. ± 3.0] and 11.5 [s.d. ± 2.9], P < 0.001). No associations were found between any of the HCPs' BMQ and patients' BMQ scores and adherence to statins. Patients' BMQ necessity, concern and necessity-concerns (NC)-differential scores were associated with patients' adherence (MARS-5) scores. B (95% CI) coefficients were 0.057 (0.035-0.079), -0.040 (-0.064 to -0.016) and.061 (0.043-0.079). CONCLUSIONS: Patients have stronger beliefs about medication compared to HCPs. No associations were found between HCPs' BMQ scores on the one hand and patients' BMQ scores and adherence to statins on the other hand.

Opening the black box of non-pharmacological care in systemic sclerosis: a cross-sectional online survey of Dutch health professionals.

The objective is to describe the spectrum of the health professional (HP) treatment approach for systemic sclerosis (SSc) from the perspective of Dutch HPs, including alignment of treatment goals set by HPs with self-reported referral reasons, coverage of patient-reported unmet care needs, and quality of communication between HPs and rheumatologists. Dutch HPs were invited through their patients with SSc to complete an anonymous online survey. The survey covered referral reasons, treatment goals, and interventions of the last patient treated, as well as the perceived quality of communication between HPs and rheumatologists. Referral reasons and treatment targets were linked to the International Classification of Functioning, Disability and Health following the refined ICF Linking Rules. Seventy-nine HPs from 8 professions (including 58 physiotherapists, 73%) completed the survey. One hundred and thirty-three different referral reasons were reported, yielding 58 different ICF codes, with 41 (70.7%) being linked to the ICF domain "body structures and functions." The reported interventions focused on body functions/structures (27.9%), training of daily activities (25.6%), education and advice (26.3%), and psychosocial interventions (20.2%). The quality of communication between HPs and rheumatologists was perceived as low. Our findings revealed numerous treatment options offered by Dutch HPs addressing the unmet care needs of patients with SSc. There is an overlap in the content of the various HP disciplines, and HP treatment goals are not sufficiently aligned with referrals of rheumatologists. HP treatment offer seemed inefficiently organized, possibly precluding rheumatologists from making targeted referrals. Communication between rheumatologists and HPs should be improved.

Use and usability of the dr. Bart app and its relation with health care utilisation and clinical outcomes in people with knee and/or hip osteoarthritis.

BACKGROUND: Self-management is of paramount importance in the non-surgical treatment of knee/hip osteoarthritis (OA). Modern technologies offer the possibility of 24/7 self-management support. We developed an e-self-management application (dr. Bart app) for people with knee/hip OA. The aim of this study was to document the use and usability of the dr. Bart app and its relation with health care utilisation and clinical outcomes in people with knee/hip OA. METHODS: For this study we used backend data for the first 26 weeks of use by the intervention group (N = 214) of an RCT examining the effectiveness of the dr. Bart app. A central element of the dr. Bart app is that it proposes a selection of 72 preformulated goals for health behaviours based on the 'tiny habits method' (e.g. after lunch I rise 12 times from my chair to train my leg muscles). The usability of the app was measured using the System Usability Scale questionnaire (SUS), on a scale of 0-100. To assess the association between the intensity of use of the app and health care utilisation (i.e., consultations in primary or secondary health care) and clinical outcomes (i.e., self-management behaviour, physical activity, health-related quality of life, illness perceptions, symptoms, pain, activities of daily living) we calculated Spearman rank correlation coefficients. RESULTS: Of the 214 participants, 171 (80%) logged in at least once with 151 (71%) choosing at least one goal and 114 (53%) completing at least one goal during the 26 weeks. Of those who chose at least one goal, 56 participants (37%) continued to log in for up to 26 weeks, 12 (8%) continued to select new goals from the offered goals and 37 (25%) continued to complete goals. Preformulated goals in the themes of physical activity (e.g., performing an exercise from the exercises library in the app) and nutrition (e.g., 'eat two pieces of fruit today') were found to be most popular with users. The mean usability scores (standard deviation) at the three and six month follow-ups were 65.9 (16.9) and 64.5 (17.5), respectively. The vast majority of associations between the intensity of use of the dr. Bart app and target outcomes were weak at ρ < (-) 0.25. CONCLUSIONS: More than one-third of people with knee/hip OA who started using the app, continued to use it up to 26 weeks, though usability could be improved. Patients appear to have preferences for goals related to physical activity and nutrition, rather than for goals related to vitality and education. We found weak/no associations between the intensity of use of the dr. Bart app and health care utilisation and clinical outcomes. TRIAL REGISTRATION: (21 September 2017): Dutch Trial Register (Trial Number NTR6693/NL6505 ).

i-CONTENT tool for assessing therapeutic quality of exercise programs employed in randomised clinical trials.

OBJECTIVE: When appraising the quality of randomised clinical trial (RCTs) on the merits of exercise therapy, we typically limit our assessment to the quality of the methods. However, heterogeneity across studies can also be caused by differences in the quality of the exercise interventions (ie, 'the potential effectiveness of a specific intervention given the potential target group of patients')-a challenging concept to assess. We propose an internationally developed, consensus-based tool that aims to assess the quality of exercise therapy programmes studied in RCTs: the international Consensus on Therapeutic Exercise aNd Training (i-CONTENT) tool. METHODS: Forty-nine experts (from 12 different countries) in the field of physical and exercise therapy participated in a four-stage Delphi approach to develop the i-CONTENT tool: (1) item generation (Delphi round 1), (2) item selection (Delphi rounds 2 and 3), (3) item specification (focus group discussion) and (4) tool development and refinement (working group discussion and piloting). RESULTS: Out of the 61 items generated in the first Delphi round, consensus was reached on 17 items, resulting in seven final items that form the i-CONTENT tool: (1) patient selection; (2) qualified supervisor; (3) type and timing of outcome assessment; (4) dosage parameters (frequency, intensity, time); (5) type of exercise; (6) safety of the exercise programme and (7) adherence to the exercise programme. CONCLUSION: The i-CONTENT-tool is a step towards transparent assessment of the quality of exercise therapy programmes studied in RCTs, and ultimately, towards the development of future, higher quality, exercise interventions.

Predictive factors for treatment-related mortality and major adverse events after autologous haematopoietic stem cell transplantation for systemic sclerosis: results of a long-term follow-up multicentre study.

BACKGROUND: Autologous haematopoietic stem cell transplantation (HSCT) improves survival in systemic sclerosis (SSc) with poor prognosis, but is hampered by treatment-related mortality (TRM). OBJECTIVE: To evaluate event-free survival (EFS), TRM, response to treatment, disease progression and patient characteristics associated with events. METHODS: All patients treated with HSCT for SSc in The Netherlands until 2017 (n=92) were included. Data on skin involvement (modified Rodnan skin score (mRSS), pulmonary function (forced vital capacity (FVC) and diffusion capacity of the lungs for carbon monoxide (DLCO)), extent of interstitial lung disease on high-resolution CT using Goh scores and left ventricular ejection fraction (LVEF) were collected at baseline, 1, 2 and 5 years. Occurrence of events, defined as death or major organ failure, were collected until 2019. As control, a comparison between patients treated with cyclophosphamide (CYC) and patients with HSCT who participated in the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial was performed. RESULTS: Median follow-up was 4.6 years. EFS estimates at 5, 10 and 15 years were 78%, 76% and 66%, respectively. Twenty deaths occurred. Mean FVC, DLCO, mRSS and Goh scores all improved significantly. Disease progression occurred in 22 patients. Frequency of TRM decreased over time and occurred more often in males. Events were independently associated with male sex, LVEF <50% and older age. In ASTIS, patients treated with HSCT (n=23) 7 events occurred versus 13 in the CYC group (n=22). CONCLUSION: Our data confirm long-term efficacy of HSCT in improving survival, skin and lung involvement in SSc. Male sex, lower LVEF and older age at baseline were identified as risk factors for events.

Treatment with cyclophosphamide i.v. pulse therapy is an option for effective treatment of skin fibrosis in patients with early systemic sclerosis.

OBJECTIVES: SSc is a autoimmune disease characterized by fibrosis of the skin and internal organs. There is a lack of evidence for the efficacy of i.v. CYC pulse therapy on skin thickening. We aimed to examine the response of i.v. CYC pulse therapy on skin thickening in our cohort of SSc patients and analysed factors that predict this response. METHODS: We retrospectively evaluated the data for 143 patients with SSc from baseline to 12, 24 and 36 months. All patients were treated with at least 6 i.v. CYC pulses (750 mg/m2/month). We applied the modified Rodnan Skin Score (mRSS) to assess skin thickening. A clinically relevant response was defined as a decrease in mRSS of 5 points and 25% from baseline. Different baseline variables for predicting response on month 12 were tested in logistic regression analyses. RESULTS: Baseline characteristics of the patients with dcSSc and lcSSc were collected. Forty-three percent (n = 42) of dcSSc patients had a clinically relevant response on month 12. Non-responding on month 6 predicts non-response on month 12 (odds ratio 37.1; 95% CI 4.5, 306.4). CONCLUSION: We concluded that i.v. CYC pulse therapy should be considered as an effective treatment option for skin thickening in dcSSc patients, because 43% of this group of patients were found to have a clinically relevant response. Of the dcSSC patients who did not respond by month 6, only 29% had a response by month 12. This finding can help the physician and patient in shared decision making about whether or not to continue therapy.

How do patients with systemic sclerosis experience currently provided healthcare and how should we measure its quality?

OBJECTIVES: To gain insight into SSc patients' perspective on quality of care and to survey their preferred quality indicators. METHODS: An online questionnaire about healthcare setting, perceived quality of care (CQ index) and quality indicators, was sent to 2093 patients from 13 Dutch hospitals. RESULTS: Six hundred and fifty patients (mean age 59 years, 75% women, 32% limited cutaneous SSc, 20% diffuse cutaneous SSc) completed the questionnaire. Mean time to diagnosis was 4.3 years (s.d. 6.9) and was longer in women compared with men (4.8 (s.d. 7.3) vs 2.5 (s.d. 5.0) years). Treatment took place in a SSc expert centre for 58%, regional centre for 29% or in both for 39% of patients. Thirteen percent of patients was not aware of whether their hospital was specialized in SSc. The perceived quality of care was rated with a mean score of 3.2 (s.d. 0.5) (range 1.0-4.0). There were no relevant differences between expert and regional centres. The three prioritized process indicators were: good patient-physician interaction (80%), structural multidisciplinary collaboration (46%) and receiving treatment according to SSc guidelines (44%). Absence of disease progression (66%), organ involvement (33%) and digital ulcers (27%) were the three highest rated outcome indicators. CONCLUSION: The perceived quality of care evaluated in our study was fair to good. No differences between expert and regional centres were observed. Our prioritized process and outcome indicators can be added to indicators suggested by SSc experts in earlier studies and can be used to evaluate the quality of care in SSc.

Effectiveness of medication review on the number of drug-related problems in patients visiting the outpatient cardiology clinic: A randomized controlled trial.

AIMS: To assess the effectiveness of medication review on the number of drug-related problems (DRPs) in outpatient cardiology patients. METHODS: In this randomized controlled trial, a computer-assisted and pharmacist-led medication review with patient involvement (questionnaire and telephone call with pharmacist) was conducted in intervention patients prior to their visit to the cardiologist. The control group received usual care. Adult outpatient cardiology patients without support concerning the administration of medication, without a medication review in the past 6 months and who gave permission to access their electronic medication record were included. The primary outcome measure was the number of DRPs 1 month after the visit. Secondary outcome measures concerned the type of DRP and the type of medication involved in the DRPs. RESULTS: In total, 75 patients (mean [standard deviation, SD] age 66.0 [12.5] years, 41% female) were included. Intervention (n = 90) and control group (n = 85) were comparable at baseline. The mean (SD) number of drugs used per patient was 7.9 (3.9). After 1 month, the mean (SD) number of DRPs was 0.3 (0.7) and 0.8 (1.0) and the median (range) number of DRPs was 0 (0-4) and 0 (0-4) in the intervention group and control group, respectively (P < .001). In the intervention group, 74% of the DRPs identified at T0 were solved at T1 vs 14% in the control group. CONCLUSION: This randomized controlled trial suggests that a pharmacist-led medication review in patients with a scheduled visit to the outpatient cardiology clinic decreases the number of DRPs.

Comparison of physical activity among different subsets of patients with knee or hip osteoarthritis and the general population.

To compare the amount of physical activity (PA) among patients with different subsets of knee or hip osteoarthritis (OA) and the general population. Secondary analyses of data of subjects ≥ 50 years from four studies: a study on the effectiveness of an educational program for OA patients in primary care (n = 110), a RCT on the effectiveness of a multidisciplinary self-management program for patients with generalized OA in secondary care (n = 131), a survey among patients who underwent total joint arthroplasty (TJA) for end-stage OA (n = 510), and a survey among the general population in the Netherlands (n = 3374). The Short QUestionnaire to ASssess Health-enhancing physical activity (SQUASH) was used to assess PA in all 4 studies. Differences in PA were analysed by multivariable linear regression analyses, adjusted for age, body mass index and sex. In all groups, at least one-third of total time spent on PA was of at least moderate-intensity. Unadjusted mean duration (hours/week) of at least moderate-intensity PA was 15.3, 12.3, 18.1 and 17.8 for patients in primary, secondary care, post TJA, and the general population, respectively. Adjusted analyses showed that patients post TJA spent 5.6 h [95% CI: 1.5; 9.7] more time on PA of at least moderate-intensity than patients in secondary care. The reported amount of PA of at least moderate-intensity was high in different subsets of OA and the general population. Regarding the amount of PA in patients with different subsets of OA, there was a substantial difference between patients in secondary care and post TJA patients.