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 P... Show moreObjectives 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. Show less
BackgroundAutoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of... Show moreBackgroundAutoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis. Incomplete biochemical response is the most important risk factor for liver transplantation or liver-related mortality. First-line treatment consists of a combination of azathioprine and prednisolone. If CR is not reached, tacrolimus (TAC) or mycophenolate mofetil (MMF) can be used as second-line therapy. Both products are registered for the prevention of graft rejection in solid organ transplant recipients. The aim of this study is to compare the effectiveness and safety of TAC and MMF as second-line treatment for AIH.MethodsThe TAILOR study is a phase IIIB, multicentre, open-label, parallel-group, randomised (1:1) controlled trial performed in large teaching and university hospitals in the Netherlands. We will enrol 86 patients with AIH who have not reached CR after at least 6 months of treatment with first-line therapy. Patients are randomised to TAC (0.07 mg/kg/day initially and adjusted by trough levels) or MMF (max 2000 mg/day), stratified by the presence of cirrhosis at inclusion. The primary endpoint is the difference in the proportion of patients reaching CR after 12 months. Secondary endpoints include the difference in the proportion of patients reaching CR after 6 months, adverse effects, difference in fibrogenesis, quality of life and cost-effectiveness.DiscussionThis is the first randomised controlled trial comparing two second-line therapies for AIH. Currently, second-line treatment is based on retrospective cohort studies. The rarity of AIH is the main issue in clinical research for alternative treatment options. The results of this trial can be implemented in existing international clinical guidelines.Trial registrationClinicalTrials.gov NCT05221411. Retrospectively registered on 3 February 2022; EudraCT number 2021-003420-33. Prospectively registered on 16 June 2021. Show less
Background The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) with compression ultrasonography (CUS) may be hindered by residual intravascular obstruction after previous DVT. A... Show moreBackground The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) with compression ultrasonography (CUS) may be hindered by residual intravascular obstruction after previous DVT. A reference CUS, an additional ultrasound performed at anticoagulant discontinuation, may improve the diagnostic work-up of suspected recurrent ipsilateral DVT by providing baseline images for future comparison.Objectives To evaluate the cost-effectiveness of routinely performing reference CUS in DVT patients.Methods Patient-level data (n 1/4 96) from a prospective management study (Theia study; NCT02262052) and claims data were used in a decision analytic model to compare 12 scenarios for diagnostic management of suspected recurrent ipsilateral DVT. Estimated health care costs and mortality due to misdiagnosis, recurrent venous thromboembolism, and bleeding during the first year of follow-up after presentation with suspected recurrence were compared.Results All six scenarios including reference CUS had higher estimated 1-year costs (1,763-1,913) than the six without reference CUS (1,192-1,474). Costs were higher because reference CUS results often remained unused, as 20% of patients (according to claims data) would return with suspected recurrent DVT. Estimated mortality was comparable in scenarios with (14.8-17.9 per 10,000 patients) and without reference CUS (14.0-18.5 per 10,000). None of the four potentially most desirable scenarios included reference CUS. Conclusion One-year health care costs of diagnostic strategies for suspected recurrent ipsilateral DVT including reference CUS are higher compared to strategies without reference CUS, without mortality benefit. These results can inform policy-makers regarding use of health care resources during follow-up after DVT. From a cost-effectiveness perspective, the findings do not support the routine application of reference CUS. Show less
Ghariq, M.; Hout, W.B. van den; Dekkers, O.M.; Bootsma, M.; Groot, B. de; Groothuis, J.G.J.; ... ; SYNERGY Consortium 2023
Background Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology ... Show moreBackground Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) Syncope Guidelines regarding diagnostic yield, accuracy and costs. Methods A multicentre pre-post study in fve Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to defne a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician’s diagnosis with the reference diagnosis. Results We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the diference 6 to 19%). Syncope-related healthcare costs did not difer between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving €908 per patient; 95% CI €34 to €1782). Conclusions ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs Show less
BackgroundAlthough reduced work ability is a substantial problem among people with inflammatory arthritis (IA), work ability is an underexposed area in clinical practice. Evidence on vocational... Show moreBackgroundAlthough reduced work ability is a substantial problem among people with inflammatory arthritis (IA), work ability is an underexposed area in clinical practice. Evidence on vocational interventions in IA is limited, but favourable results of delivery by a physiotherapist (PT) warrant the need for further research. Therefore, we aim to evaluate the (cost-)effectiveness of a multimodal, PT-led, vocational intervention in (self-)employed people with IA compared to usual care.MethodsThis randomized controlled trial will include 140 people with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) who are (self-)employed and have reduced work ability (Work Ability Index – Single Item Scale (WAS) ≤ 7/10) and/or RA/axSpA related sick leave (≤ 6 months). Participants will be randomized 1:1 to the intervention or control condition (usual care). The intervention, delivered by primary care PTs, will be personalized to each patient, consisting of 10 to 21 sessions over 12 months. The intervention will be multimodal, comprising of 1) exercise therapy and a physical activity plan, 2) education/self-management support, 3) work-roadmap to guide participants in finding relevant other care, with optionally 4) online self-management course and 5) workplace examination. Assessments will be performed at baseline and after 3, 6, and 12 months. The primary outcome measure of effectiveness is work ability, as measured with the WAS at 12 months. For the cost-effectiveness analysis, the EuroQol (EQ-5D-5L), self-reported healthcare use, sick leave and productivity while at work will be used to estimate the trial based cost-utility from a societal perspective. A process evaluation, including assessments of adherence and treatment fidelity, will be undertaken using the registrations of the PTs and semi-structured interviews at 12 months follow-up in a random sample of the intervention group.DiscussionThe results of this study will provide insights in the (cost-)effectiveness of a multimodal, PT-led, vocational intervention in people with IA and a reduced work ability. Show less
