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PURPOSE: The primary aim of our study was to identify the absolute incidence and implant survival of multiply revised knee arthroplasties based on nationwide register data. The secondary aim was to determine the change in the absolute incidence and implant survival of multiply revised knee arthroplasties Methods: We performed a retrospective observational study of primary knee arthroplasties using several nationwide Danish registers. All primary knee arthroplasties performed in Denmark from 1998 to 2021 were identified. From these primary arthroplasties, revision procedures were identified. Kaplan-Meier plots were used in survival analysis to estimate the likelihood of implant survival. RESULTS: 161,384 primary knee arthroplasties and their revisions performed between 1998 and 2021 were identified; of 13,786 (8.5%) revisions there were 10,638 1st revisions, 2,148 2nd revisions, 624 3rd revisions, 223 4th revisions, and 153 procedures that had been revised more than 4 times. The 10-year revision-free survival of primary arthroplasties was 92.3% (95% confidence interval [CI] 92.2-92.5). First-time revisions had a 10-year revision-free survival of 75.9% (CI 74.9-76.9). The 10-year survival of second- and third-time revisions was 65.1% (CI 62.6-67.6) and 57.8% (CI 53.4-62.5), respectively. The 10-year implant survival probabilities of primary knee arthroplasties were 91.4% in 1998-2009 and 93.3% in 2010-2021 (difference 2.2%). The 10-year implant survival probabilities of 1st revisions were 77% in 1998-2009 and 75% in 2010-2021 (difference -2.4%). CONCLUSION: We found that 0.3% of all primary knee arthroplasties resulted in 3 or more revisions. The implant survival decreased for each consecutive revision, with almost half of the 3rd revisions being re-revised within 10 years. The 10-survival of the primary implant was higher in 2010-2021, and the 10-year survival of the 1st revision was higher in 1998-2009.
Subject(s)
Arthroplasty, Replacement, Knee , Prosthesis Failure , Registries , Reoperation , Humans , Arthroplasty, Replacement, Knee/statistics & numerical data , Arthroplasty, Replacement, Knee/mortality , Reoperation/statistics & numerical data , Denmark/epidemiology , Female , Male , Retrospective Studies , Aged , Incidence , Middle Aged , Knee Prosthesis , Aged, 80 and over , Adult , Kaplan-Meier EstimateABSTRACT
INTRODUCTION: The absence of reliable prognostic markers poses a challenge to the management of inflammatory bowel disease (IBD). Patients with aggressive disease may not receive sufficient treatment with conventional 'step-up' therapy, whereas a top-down approach may expose patients with indolent disease to unnecessary treatment-related toxicity. The objective of the Nordic IBD treatment strategy trial (NORDTREAT) is to assess the feasibility of personalised therapy by stratifying patients according to a prognostic serum protein signature at diagnosis. METHODS AND ANALYSIS: NORDTREAT is a multicentre, biomarker-strategy design, open-label controlled trial. After screening consent, eligible patients are randomised (1:1) into one of two groups: a group with access to the protein signature and a group without access. In the access to protein signature group, patients displaying a protein signature suggestive of an increased risk of an aggressive disease course will be treated in line with a top-down treatment algorithm (anti-tumour necrosis factor agent with/without an immunomodulator). In contrast, those with a protein signature indicative of indolent disease will be excluded from the trial. Patients not in the access group receive treatment based on clinical management. This traditional management involves a stepwise escalation of treatment as determined by the investigator after failure of first-line treatment. After 52 weeks, outcomes are assessed in the subgroup of patients with a protein profile indicating a potentially severe disease trajectory. The primary endpoint is a composite of the proportion of patients with corticosteroid-free clinical and endoscopic remission at week 52. Surgical intervention due to IBD during follow-up will be defined as treatment failure. ETHICS AND DISSEMINATION: Ethical approval has been obtained, and recruitment is underway at sites in four participating Nordic countries (Denmark, Iceland, Norway and Sweden). Following trial completion and data analysis, the trial results will be submitted for publication in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT05180175; Pre-results. EudraCT number: 2019-002942-19.
Subject(s)
Biomarkers , Inflammatory Bowel Diseases , Humans , Biomarkers/blood , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/therapy , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Prognosis , Precision Medicine/methods , Scandinavian and Nordic Countries , Immunologic Factors/therapeutic useABSTRACT
Background: The high incidence of knee injuries in football/handball challenges effective prevention. Identifying tangible and modifiable factors associated with a knee injury may innovate preventive actions. Engaging key stakeholders can reveal crucial insights that could improve knee injury prevention in football/handball. Objective: To investigate football/handball stakeholders' perspectives on reasons for acute and severe knee injuries to generate a conceptual model on important factors associated with knee injuries in football/handball. Methods: Mixed-method participatory Group Concept Mapping was applied to collect statements from football/handball stakeholders (players/coaches/healthcare staff/researchers) on the question, 'What may explain why some players sustain a knee injury?'. Participants rated the importance and feasibility of screening for each statement. Multidimensional scaling and hierarchical cluster analysis produced a cluster map, forming the basis for developing a final conceptual model. Results: Stakeholders (n=37) generated and sorted 100 statements. Cluster analysis followed by cluster map validation yielded seven themes: (1) the player's physical and motor skill profile, (2) preparation and training, (3) footwear and playing surface, (4) the sport's impact on the risk of injury, (5) mental and physical fatigue, (6) history of injury and 7) genetics and context. A final conceptual model illustrating factors associated with knee injuries in football/handball was developed. Forty-six statements were identified as both important and feasible to screen for. Conclusions: Stakeholders' perspectives on knee injuries in football/handball revealed a complex interplay of factors. We developed a conceptual model fostering stakeholder dialogue for enhanced prevention. Key among its themes is 'preparation and training'.
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The prevalence and disease burden of chronic inflammatory diseases (CIDs) are predicted to rise. Patients are commonly treated with biological agents, but the individual treatment responses vary, warranting further research into optimizing treatment strategies. This study aimed to compare the clinical treatment responses in patients with CIDs initiating biologic therapy based on smoking status, a notorious risk factor in CIDs. In this multicentre cohort study including 233 patients with a diagnosis of Crohn's disease, ulcerative colitis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis or psoriasis initiating biologic therapy, we compared treatment response rates after 14 to 16 weeks and secondary outcomes between smokers and non-smokers. We evaluated the contrast between groups using logistic regression models: (i) a "crude" model, only adjusted for the CID type, and (ii) an adjusted model (including sex and age). Among the 205 patients eligible for this study, 53 (26%) were smokers. The treatment response rate among smokers (n = 23 [43%]) was lower compared to the non-smoking CID population (n = 92 [61%]), corresponding to a "crude" OR of 0.51 (95% CI: [0.26;1.01]) while adjusting for sex and age resulted in consistent findings: 0.51 [0.26;1.02]. The contrast was apparently most prominent among the 38 RA patients, with significantly lower treatment response rates for smokers in both the "crude" and adjusted models (adjusted OR 0.13, [0.02;0.81]). Despite a significant risk of residual confounding, patients with CIDs (rheumatoid arthritis in particular) should be informed that smoking probably lowers the odds of responding sufficiently to biological therapy. Registration: Clinical.Trials.gov NCT03173144.
Subject(s)
Arthritis, Rheumatoid , Biological Products , Smoking , Humans , Male , Female , Middle Aged , Adult , Prospective Studies , Smoking/adverse effects , Biological Products/therapeutic use , Treatment Outcome , Arthritis, Rheumatoid/drug therapy , Psoriasis/drug therapy , Colitis, Ulcerative/drug therapy , Chronic Disease , Crohn Disease/drug therapy , Cohort Studies , Arthritis, Psoriatic/drug therapy , Aged , InflammationABSTRACT
To evaluate tumour necrosis factor inhibitor (TNFi) drug-levels and presence of anti-drug antibodies (ADAb) in patients with inflammatory arthritis who taper TNFi compared to TNFi continuation. Patients with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis on stable TNFi dose and in low disease activity ≥ 12 months were randomised (2:1) to disease activity-guided tapering or control. Blood samples at baseline, 12- and 18-months were evaluated for TNFi drug-levels and ADAb. In total, 129 patients were randomised to tapering (n = 88) or control (n = 41). Between baseline and month 18, a significant shift in TNFi drug-levels were observed in the tapering group resulting in fewer patients with high drug-levels (change: - 14% [95% CI - 27 to - 1%]) and more with low drug-levels (change: 18% [95% CI 5-31%]). Disease activity was equivalent between groups at 18 months, mean difference: RA - 0.06 (95% CI - 0.44 to 0.33), PsA 0.03 (95% CI - 0.36 to 0.42), and axSpA 0.16 (- 0.17 to 0.49), equivalence margins ± 0.5 disease activity points. ADAb were detected in eight patients, all from the tapering group. TNFi drug-level category or ADAb were not predictive for achieving successful tapering at 18 months. TNFi drug-levels decreased during tapering which indicate adherence to the tapering algorithm. Despite the difference in TNFi drug-levels at 18 months, disease activity remained equivalent, and only few tapering patients had detectable ADAb. These data do not support using TNFi drug-level and/or ADAb to guide the tapering decision but future research with larger trials is needed.Trial registration: EudraCT: 2017-001970-41, December 21, 2017.
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OBJECTIVE: To compare the effect of an illness perception conversation (IPC), relative to a research participation conversation (RPC), on 2-week changes in knee pain in patients with knee osteoarthritis. METHOD: This was a randomised single-blind trial. Patients were randomised to two matched conversations. An IP conversation concerning the participant's knee pain-related illness perception (IP) or an RPC concerning the participant's motivation for participating in research. Both conversations were followed by an open-label intraarticular saline injection in the most symptomatic knee. The primary outcome was change in knee pain from baseline to 2 weeks follow-up on a 100 mm visual analogue scale (VAS). Key secondary outcomes included the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales: Activities of daily living (ADL) and Quality of life (QoL). Main analyses were based on the intention-to-treat population using repeated measures mixed effects linear models. RESULTS: 103 patients were randomised to the IPC group (n = 52) and the RPC group (n = 51). VAS knee pain scores changed statistically significantly from baseline to end of treatment in both groups, -13.7 (standard error [SE]: 3.2) in the IPC group and -13.0 (SE: 3.1) in the RPC group with an adjusted between-group difference of -0.7 (95% CI: -8.3 to 6.9; P = 0.85). Likewise, no group differences were seen in KOOS ADL and KOOS QoL. CONCLUSION: A conversation concerning knee pain-related IP did not augment the pain-relieving effect of an open-label placebo injection when compared to a similar control conversation concerning motivations for participating in research. TRIAL REGISTRATION: NCT05225480.
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OBJECTIVES: To explore which core domain is best associated with the American College of Rheumatology (ACR) 20% response in trials assessing the effect of targeted interventions in rheumatoid arthritis (RA). METHODS: A meta-epidemiological study was performed on randomised trials investigating biologics and targeted agents compared with placebo or conventional disease-modifying antirheumatic drugs in patients with RA. The main outcome measures were ORs for the ACR 20% response and at least one of the eight core domains according to the existing RA core outcome set (COS) analysed based on standardised mean differences. RESULTS: 115 trials involving 55 422 patients with RA were eligible. The OR for achieving ACR 20% response was 3.19 (95% CI 2.96 to 3.44) for the experimental interventions relative to the comparators. The median number of COS domains reported was 6; 18 trials reported only 1 domain, 17 all 8. Univariable meta-regression analyses indicated that each of the eight core domains was significantly associated with ACR 20% response, yet improvements in physical disability explain a successful ACR 20% response the most. Including only trials reporting on all eight core domains, univariable meta-regression analyses proved improvement in fatigue to explain a successful ACR 20% response the most. CONCLUSIONS: Within this dataset, it is evident that the conclusions concerning our primary objective were significantly influenced by both the amount and characteristics of missing data. Our data suggest that fatigue could be more important for the primary endpoint than previously assumed, but this is based on limited data.
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Background: Elite endurance training is characterised by a high-volume load of the heart and has been associated with atrial fibrillation (AF) in middle-aged men. We compared left atrial (LA) remodelling among elite athletes engaged in sports, categorised as having low, intermediate, and high cardiac demands. Methods: This cross-sectional echocardiographic study of healthy elite athletes evaluated LA size and function measured as LA maximum volume (maxLAVi) and contraction strain. Athletes were grouped according to the cardiac demands of their sport (low, intermediate, high). Morphological measures were indexed to body surface area and reported as least square means; differences between groups were reported with 95% CIs. Results: We included 482 elite athletes (age 21±5 years (mean±SD), 39% women). MaxLAVi was larger in the high group (28.4 mL/m2) compared with the low group (20.2 mL/m2; difference: 8.2, CI 5.3 to 11.1 mL/m2; p<0.001), where measurements in men exceed those in women (26.4 mL/m2 vs 24.7 mL/m2; difference 1.6 mL/m2; CI 0.3 to 2.9 mL/m2; p=0.0175). In the high group, LA contraction strain was lower compared with the low group (-10.1% vs -12.9%; difference: 2.8%; CI 1.3 to 4.3%; p<0.001), and men had less LA contraction strain compared with women (-10.3% vs -11.0%; difference 0.7%; CI 0.0 to 1.4%; p=0.049). Years in training did not affect maxLAVi or LA contraction strain. Conclusion: MaxLAVi was higher while LA contraction strain was lower with increased cardiac demands. MaxLAVi was larger, and LA contraction was lower in men compared with women. Whether these sex-based differences in LA remodelling are a precursor to pathological remodelling in male athletes is unknown.
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INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is 'severe IBD' within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death. METHODS AND ANALYSIS: We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits. ETHICS AND DISSEMINATION: This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. CLINICAL TRIAL REGISTRATION NUMBER: NCT05414578; Pre-results.
Subject(s)
Biomarkers , Inflammatory Bowel Diseases , Humans , Crohn Disease/diagnosis , Crohn Disease/therapy , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/therapy , Longitudinal Studies , Multicenter Studies as Topic , Prognosis , Prospective Studies , Research Design , Scandinavian and Nordic CountriesABSTRACT
OBJECTIVE: To assess the effect of proton pump inhibitor (PPI) use on bone mineral density (BMD) and bone microarchitecture as measured by the trabecular bone score (TBS) in patients with inflammatory rheumatic and musculoskeletal diseases (iRMDs). METHODS: Cross-sectional data from a prospective single-center cohort (2015 to 2022) of patients with iRMDs were used to evaluate 3 co-primary outcomes: BMD of the left femoral neck and the lumbar spine (as T-scores) and the TBS. Inverse probability weighting adjusted for numerous confounders including age, sex, body mass index, current and cumulative glucocorticoid (GC) dose, C-reactive protein levels, disability, and others. Analyses were based on general linear models, following a prespecified statistical analysis plan. RESULTS: The study included 1495 patients (75% women; mean age, 62.6±13.1 years; 49% and 63% with regular PPI and GC use, respectively). The PPI users had lower BMD at both spine (adjusted contrast -0.25; 95% CI, -0.47 to -0.04; P=.02) and femoral neck (-0.17 [-0.35 to 0.01]; P=.07). Differences between PPI users and nonusers were statistically significant only in patients concurrently using GCs at more than 7.5 mg/d prednisone equivalent. The TBS was similar in PPI users and nonusers (adjusted contrast, 0.00 [-0.04 to 0.04]; P=.97). CONCLUSION: Our results suggest that PPIs lead to a loss of BMD rather than an impairment of bone microarchitecture in patients with iRMDs. The negative association between PPI use and BMD appears to be dependent on concurrent GC use. Clinicians should carefully review the indication for PPI use in patients with iRMDs, especially in those receiving higher dose GCs.
Subject(s)
Bone Density , Proton Pump Inhibitors , Rheumatic Diseases , Humans , Proton Pump Inhibitors/adverse effects , Proton Pump Inhibitors/administration & dosage , Female , Male , Cross-Sectional Studies , Middle Aged , Bone Density/drug effects , Rheumatic Diseases/drug therapy , Rheumatic Diseases/complications , Prospective Studies , Aged , Glucocorticoids/adverse effects , Glucocorticoids/administration & dosage , Femur Neck/diagnostic imaging , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/diagnostic imagingSubject(s)
Biomarkers , Cholesterol, LDL , Humans , Cholesterol, LDL/blood , Biomarkers/blood , Cardiovascular Diseases/bloodABSTRACT
OBJECTIVES: There is growing interest in collecting outcome information directly from patients in clinical trials. This study evaluates what patients with rheumatic and musculoskeletal diseases (RMDs) consider important to know about symptomatic side effects they may experience from a new prescription drug. METHODS: Patients with inflammatory arthritis, who had one or more prescribed drugs for their disease for at least 12 months, participated in focus groups and individual interviews. Discussions were analysed using reflexive thematic analysis. RESULTS: We conducted seven focus groups with 34 participants across three continents. We found four overarching and two underpinning themes. The 'impact on life' was connected to participants 'daily life', 'family life', 'work life', and 'social life'. In 'psychological and physical aspects' participants described 'limitation to physical function', 'emotional dysregulation' and 'an overall mental state'. Extra tests, hospital visits and payment for medication were considered a 'time, energy and financial burden' of side effects. Participants explained important measurement issues to be 'severity', 'frequency', and 'duration'. Underpinning these issues, participants evaluated the 'benefit-harm-balance' which includes 'the cumulative burden' of having several side effects and the persistence of side effects over time. CONCLUSIONS: In treatment for RMDs, there seems to be an urgent need for feasible measures of patient-reported bother (impact on life and cumulative burden) from side effects and the benefit-harm-balance. These findings contribute new evidence in support of a target domain-an outcome that represents the patient voice evaluating the symptomatic treatment-related side effects for people with RMDs enrolled in clinical trials.
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OBJECTIVE: To determine the diagnostic accuracy of thoracic ultrasound (TUS) for detecting interstitial lung disease (ILD) in rheumatoid arthritis (RA) with respiratory symptoms. METHODS: Individuals with RA visiting rheumatologic outpatient clinics in the Region of Southern Denmark were systematically screened for dyspnea, cough, recurrent pneumonia, prior severe pneumonia, or a chest x-ray indicating interstitial abnormalities. Eighty participants with a positive screening were consecutively included. Individuals were not eligible if they had a chest high-resolution computed tomography (HRCT) less than 12 months ago or were already diagnosed with ILD. A blinded TUS expert evaluated TUS, and TUS was registered as positive for ILD if at least 10 B-lines or bilateral thickened and fragmented pleura were present. The primary outcomes were TUS's sensitivity, specificity, and positive predictive value and negative predictive value. An ILD-specialized thoracic radiologist assessed HRCT, followed by a multidisciplinary team discussion, which was the reference standard. The accepted window of HRCT was less than 30 days after TUS was performed. RESULTS: A total of 77 participants received HRCT less than 30 days after TUS, and 23 (30%) were diagnosed with ILD. TUS had a sensitivity of 82.6% (95% confidence interval [CI] 61.2%-95.0%) and a specificity of 51.9% (95% CI 37.8%-65.7%), corresponding to a positive predictive value of 42.2% (95% CI 27.7%-57.8%) and a negative predictive value of 87.5% (95% CI 71.0%-96.5%). CONCLUSION: To our knowledge, this prospective study is the first to use respiratory symptoms in RA as inclusion criteria. Systematic screening for respiratory symptoms combined with TUS can reduce the diagnostic delay of ILD in RA.
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OBJECTIVE: To examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors. METHODS: We systematically searched PubMed, EMBASE and CENTRAL from inception to December 26, 2021. We included randomised controlled trials of people with hand osteoarthritis with a placebo or an untreated control group. We assessed the Risk of Bias with Cochrane Risk-of-Bias tool version 2. Each comparator was contrasted with a null-arm, imputed as having a zero change from baseline with the same standard deviation as the comparator. We combined the standardised mean differences with a random effects meta-analysis. The contextual factors' effect was explored in meta-regression and stratified models with pain as the dependent variable. RESULTS: 84 trials (7262 participants) were eligible for quantitative synthesis, of which 76 (6462 participants) were eligible for the stratified analyses. Placebos were superior to their matched null-arms in relieving pain with an effect size of -0.51 (95% confidence interval -0.61 to -0.42), while untreated control groups were not. When analysing all comparators, blinded trial designs and low risk of bias were associated with higher pain relief compared to an open-label trial design and some concern or high risk of bias. CONCLUSION: The placebo response on pain for people with hand osteoarthritis was increased by appropriate blinding and a lower risk of bias assessment. Placebos were superior to a null-arm, while untreated control groups were not. Results emphasise the importance of using appropriate comparators in clinical trials. PROSPERO REGISTRATION ID: CRD42022298984.
Subject(s)
Hand Joints , Osteoarthritis , Randomized Controlled Trials as Topic , Humans , Control Groups , Hand Joints/physiopathology , Osteoarthritis/drug therapy , Placebos/therapeutic useABSTRACT
BACKGROUND: Adipose-derived mesenchymal stem/stromal cells (ASCs) are proposed as a new xerostomia treatment. The study evaluated the long-term safety and effectiveness of allogeneic ASCs in radiation-induced xerostomia among patients with previous oropharyngeal cancer. METHODS: This study constitutes 3-year follow-up on the original 10 patients who received allogeneic ASCs injections to the submandibular and parotid glands as part of the MESRIX-II trial. The MESRIX-II trial included the preliminary 4-month follow-up. The primary endpoint was long-term safety. Secondary endpoints were effectiveness evaluated by changes in salivary flow rate and patient-reported outcomes (PROs). Immune response was evaluated by assessing the development of donor-specific antibodies (DSA). FINDINGS: All 10 MESRIX-II patients completed the long-term follow-up (ie, no missing data). During the long-term follow-up, 2 patients encountered a significant adverse event, which was determined to be unrelated to the treatment. No DSAs were detectable at 3 years. The stimulated salivary flow rate increased significantly from an average of 0.66 mL/minute at baseline to 0.86 mL/minute at follow-up, corresponding to an increase of 0.20 [95% CI 0.08 to 0.30] mL/minute, or approximately 30%. Among the PROs, sticky saliva symptoms were reduced, with a -20.0 [95% CI -37.3 to -2.7] units. INTERPRETATION: In conclusion, this study is the first to present long-term follow-up outcomes of allogeneic ASC treatment as a therapeutic option for radiation-induced xerostomia. The study found that ASC treatment appears safe, and there were no indications of adverse immune responses at the 3-year follow-up. Further studies are warranted to evaluate the findings in larger settings.
Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Xerostomia , Humans , Xerostomia/etiology , Xerostomia/therapy , Mesenchymal Stem Cell Transplantation/methods , Male , Female , Middle Aged , Aged , Mesenchymal Stem Cells/cytology , Follow-Up Studies , Transplantation, Homologous/methods , Treatment OutcomeABSTRACT
OBJECTIVE: To investigate whether a 2-year MRI treat-to-target strategy targeting the absence of osteitis combined with clinical remission, compared with a conventional treat-to-target strategy targeting clinical remission only (IMAGINE-rheumatoid arthritis (RA) trial) improves clinical and radiographic outcomes over 5 years in patients with RA in clinical remission. METHODS: IMAGINE-more was an observational extension study of the original 2-year IMAGINE-RA randomised trial (NCT01656278). Clinical examinations and radiographs (hands and feet) were obtained yearly. Prespecified coprimary outcomes at year 5 were Disease Activity Score in 28 joints C reactive protein (DAS28-CRP) remission rate (DAS28-CRP<2.6) and no radiographic progression (van der Heijde-modified Sharp score (vdHSS) ≤0) from baseline. Secondary outcomes included 5-year changes in radiographic, MRI and clinical measures of disease activity and physical function. RESULTS: In total 131 patients, 86 women (67%), mean age 61.2, disease duration 9.5 years, median baseline DAS28-CRP 1.9 (IQR 1.6-2.2) and vdHSS 16.0 (IQR 7.0-36.0) were included in the study; 59 (59%) patients from the original MRI treat-to-target group and 72 (72%) from the conventional group. At year 5, 47 patients (80%) in the MRI treat-to-target group vs 54 patients (75%) in the conventional treat-to-target group were in DAS28-CRP remission (OR 2.00 (95% CI 0.76 to 5.28); p=0.16) while 14 patients (24%) vs 19 patients (26%) had no radiographic progression (OR 0.70, (95% CI 0.28 to 1.71); p=0.43). CONCLUSION: A 2-year combined MRI and clinical treat-to-target strategy, compared with a conventional clinical treat-to-target strategy alone, had no effect on the long-term probability of achieving DAS28-CRP remission and of avoiding radiographic progression.