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- Hetland, M. L., et al.
(author)
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Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial
- 2020
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In: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 371
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Journal article (peer-reviewed)abstract
- OBJECTIVE To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. DESIGN Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. SETTING Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. PARTICIPANTS Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. INTERVENTIONS Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. MAIN OUTCOME MEASURES The primary outcome was adjusted clinical disease activity index remission (CDAI <= 2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms. RESULTS 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. CONCLUSIONS All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.
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- Knoop, J., et al.
(author)
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Improvement in upper leg muscle strength underlies beneficial effects of exercise therapy in knee osteoarthritis: secondary analysis from a randomised controlled trial
- 2015
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In: Physiotherapy. - : Elsevier BV. - 0031-9406. ; 101:2, s. 171-177
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Journal article (peer-reviewed)abstract
- Objectives Although exercise therapy is effective for reducing pain and activity limitations in patients with knee osteoarthritis (OA), the underlying mechanisms are unclear. This study aimed to evaluate if improvements in neuromuscular factors (i.e. upper leg muscle strength and knee proprioception) underlie the beneficial effects of exercise therapy in patients with knee OA. Design Secondary analyses from a randomised controlled trial, with measurements at baseline, 6 weeks, 12 weeks and 38 weeks. Participants One hundred and fifty-nine patients diagnosed with knee OA. Main outcome measures Changes in pain [numeric rating scale (NRS)] and activity limitations [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function subscale and get-up-and-go test] during the study period. Independent variables were changes in upper leg muscle strength and knee joint proprioception (i.e. motion sense) during the study period. Longitudinal regression analyses (generalised estimating equation) were performed to analyse associations between changes in upper leg muscle strength and knee proprioception with changes in pain and activity limitations. Results Improved muscle strength was significantly associated with reductions in NRS pain {B coefficient 2.5 [95% confidence interval (CI) -3.7 to -1.4], meaning that every change of 1 unit of strength was linked to a change of 2.5 units of pain}, WOMAC physical function (-8.8, 95% CI -13.4 to -4.2) and get-up-and-go test (-1.7, 95% CI 2.4 to 1.0). Improved proprioception was not significantly associated with better outcomes of exercise therapy (P > 0.05). Conclusions Upper leg muscle strengthening is one of the mechanisms underlying the beneficial effects of exercise therapy in patients with knee OA. (C) 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.
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- Nooijen, C. F., et al.
(author)
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A behavioral intervention promoting physical activity in people with subacute spinal cord injury : secondary effects on health, social participation and quality of life
- 2017
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In: Clinical Rehabilitation. - : SAGE Publications. - 0269-2155 .- 1477-0873. ; 31:6, s. 772-780
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To assess, for people with subacute spinal cord injury, if rehabilitation that is reinforced with the addition of a behavioral intervention to promote physical activity leads to a better health, participation and quality of life. DESIGN: Randomized controlled trial. SETTING: Rehabilitation centers. PARTICIPANTS: A total of 39 participants analyzed (45 included), with subacute spinal cord injury in inpatient rehabilitation, dependent on a manual wheelchair (33% tetraplegia, 62% motor complete, 150 +/-74 days postinjury). INTERVENTION: A behavioral intervention promoting physical activity after discharge, involving 13 individual sessions delivered by a coach trained in motivational interviewing, beginning two months before and ending six months after discharge from inpatient rehabilitation. MAIN MEASURES: Physical capacity as determined during a maximal exercise test, body mass index, blood pressure, fasting lipid profile, and social participation (IMPACT-S) and quality of life (SF-36) were determined using questionnaires. Measurements were performed two months before discharge, at discharge, and six and 12 months after discharge from inpatient rehabilitation. B represents the between-group difference. RESULTS: Twelve months after discharge, significant intervention effects were found for diastolic blood pressure (B = -11.35 mmHg, 95% CI = -19.98 to -2.71), total cholesterol (B = -0.89 mmol/L, 95% CI = -1.59 to -0.20), low-density lipoprotein cholesterol (B = -0.63 mmol/L, 95% CI = -1.25 to -0.00) and participation (B = 9.91, 95% CI = 3.34 to 16.48). CONCLUSIONS: A behavioral intervention promoting physical activity after discharge from inpatient rehabilitation improves social participation and seems to reduce risk factors for cardiovascular disease in people with subacute spinal cord injury.
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- Nooijen, Carla F., et al.
(author)
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A behavioural intervention increases physical activity in people with subacute spinal cord injury : a randomised trial
- 2016
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In: Journal of Physiotherapy. - : Elsevier BV. - 1836-9553 .- 1836-9561. ; 62:1, s. 35-41
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Journal article (peer-reviewed)abstract
- QUESTIONS: For people with subacute spinal cord injury, does rehabilitation that is reinforced with the addition of a behavioural intervention to promote physical activity lead to a more active lifestyle than rehabilitation alone? DESIGN: Randomised, controlled trial with concealed allocation, intention-to-treat analysis, and blinded assessors. PARTICIPANTS: Forty-five adults with subacute spinal cord injury who were undergoing inpatient rehabilitation and were dependent on a manual wheelchair. The spinal cord injuries were characterised as: tetraplegia 33%; motor complete 62%; mean time since injury 150 days (SD 74). INTERVENTION: All participants received regular rehabilitation, including handcycle training. Only the experimental group received a behavioural intervention promoting an active lifestyle after discharge. This intervention involved 13 individual sessions delivered by a coach who was trained in motivational interviewing; it began 2 months before and ended 6 months after discharge from inpatient rehabilitation. OUTCOME MEASURES: The primary outcome was physical activity, which was objectively measured with an accelerometer-based activity monitor 2 months before discharge, at discharge, and 6 and 12 months after discharge from inpatient rehabilitation. The accelerometry data were analysed as total wheeled physical activity, sedentary time and motility. Self-reported physical activity was a secondary outcome. RESULTS: The behavioural intervention significantly increased wheeled physical activity (overall between-group difference from generalised estimating equation 21minutes per day, 95% CI 8 to 35). This difference was evident 6 months after discharge (28minutes per day, 95% CI 8 to 48) and maintained at 12 months after discharge (25minutes per day, 95% CI 1 to 50). No significant intervention effect was found for sedentary time or motility. Self-reported physical activity also significantly improved. CONCLUSION: The behavioural intervention was effective in eliciting a behavioural change toward a more active lifestyle among people with subacute spinal cord injury. TRIAL REGISTRATION: NTR2424.
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- Nooijen, C. F., et al.
(author)
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Working mechanisms of a behavioural intervention promoting physical activity in persons with subacute spinal cord injury
- 2016
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In: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 48:7, s. 583-8
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Journal article (peer-reviewed)abstract
- OBJECTIVE: In order to unravel the working mechanisms that underlie the effectiveness of a behavioural intervention promoting physical activity in persons with subacute spinal cord injury, the aim of this study was to assess the mediating effects of physical and psychosocial factors on the intervention effect on physical activity. DESIGN: Randomized controlled trial. SETTING: Four rehabilitation centres in the Netherlands. SUBJECTS: Thirty-nine persons with subacute spinal cord injury. INTERVENTION: Behavioural intervention promoting an active lifestyle, based on motivational interviewing. The intervention involved a total of 13 individual sessions beginning 2 months before and ending 6 months after discharge from initial inpatient rehabilitation. MAIN MEASURES: The potential mediating effects of fatigue, pain, depression, illness cognition, exercise self-efficacy, coping and social support on the effect of the behavioural intervention on objectively measured physical activity (B = 0.35 h, p < 0.01) were studied. Measurements were performed at baseline, discharge, 6 months and 1 year after discharge. RESULTS: No single factor was found that strongly mediated the effect of the behavioural intervention on physical activity; however, multiple factors could partly explain the effect. Mediating effects greater than 10% were found for proactive coping (17.6%), exercise self-efficacy (15.9%), pain disability (15.3%) and helplessness (12.5%). DISCUSSION: Proactive coping (the ability to anticipate and deal with potential threats before they occur), exercise self-efficacy (self-confidence with respect to performing exercise and daily physical activities), pain disability (interference by pain of daily activities) and helplessness (emphasizing the aversive meaning of the disease) are important concepts in interventions promoting physical activity in persons with subacute spinal cord injury.
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- Rijzewijk, Luuk J, et al.
(author)
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Liver fat content in type 2 diabetes : relationship with hepatic perfusion and substrate metabolism.
- 2010
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:11, s. 2747-2754
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Journal article (peer-reviewed)abstract
- OBJECTIVE:Hepatic steatosis is common in type 2 diabetes. It is causally linked to the features of the metabolic syndrome, liver cirrhosis, and cardiovascular disease. Experimental data have indicated that increased liver fat may impair hepatic perfusion and metabolism. The aim of the current study was to assess hepatic parenchymal perfusion, together with glucose and fatty acid metabolism, in relation to hepatic triglyceride content.RESEARCH DESIGN AND METHODS:Fifty-nine men with well controlled type 2 diabetes and 18 age-matched healthy normoglycemic men were studied using positron emission tomography to assess hepatic tissue perfusion, insulin-stimulated glucose, and fasting fatty acid metabolism, respectively, in relation to hepatic triglyceride content, quantified by proton magnetic resonance spectroscopy. Patients were divided into two groups with hepatic triglyceride content below (type 2 diabetes-low) or above (type 2 diabetes-high) the median of 8.6%.RESULTS:Type 2 diabetes-high patients had the highest BMI and A1C and lowest whole-body insulin sensitivity (ANOVA, all P < 0.001). Compared with control subjects and type 2 diabetes-low patients, type 2 diabetes-high patients had the lowest hepatic parenchymal perfusion (P = 0.004) and insulin-stimulated hepatic glucose uptake (P = 0.013). The observed decrease in hepatic fatty acid influx rate constant, however, only reached borderline significance (P = 0.088). In type 2 diabetic patients, hepatic parenchymal perfusion (r = -0.360, P = 0.007) and hepatic fatty acid influx rate constant (r = -0.407, P = 0.007) correlated inversely with hepatic triglyceride content. In a pooled analysis, hepatic fat correlated with hepatic glucose uptake (r = -0.329, P = 0.004).CONCLUSIONS:In conclusion, type 2 diabetic patients with increased hepatic triglyceride content showed decreased hepatic parenchymal perfusion and hepatic insulin mediated glucose uptake, suggesting a potential modulating effect of hepatic fat on hepatic physiology.
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