Effectiveness and safety of polyacrylamide hydrogel injection for knee osteoarthritis: results from a 12-month follow up of an open-label study.

OBJECTIVE: There are few effective osteoarthritis (OA) therapies. A novel injectable polyacrylamide hydrogel (iPAAG) previously demonstrated efficacy and safety up to week 26 in an open-label study of knee OA. Here we report longer-term effectiveness and safety data. METHODS: This multi-centre, open-label study included patients with symptomatic and radiographic knee OA. Primary outcome was WOMAC pain (0-100 scale) at 13 weeks, and patients continued to 26 weeks before entering a further 26-week extension phase. Secondary efficacy outcomes included WOMAC stiffness and function subscales, Patient Global Assessment (PGA) and proportion of OMERACT-OARSI responders. Safety outcomes were adverse events (AEs). RESULTS: 49 participants (31 women, mean age 70) received an ultrasound-guided, intra-articular injection of 6 ml iPAAG; 46 completed the extension phase to 52 weeks. There was a significant reduction in the WOMAC pain score from baseline to 52 weeks (- 17.7 points (95% CI - 23.1; - 12.4); p < 0.0001). Similar sustained improvements were observed for WOMAC stiffness (11.0 points; 95% CI - 17.0; - 4.9), physical function (18.0 points; 95% CI - 19.1; - 10.6), and PGA (16.3 points; 95% CI - 23.1; - 9.4). At 52 weeks 62.2% of patients were OMERACT-OARSI responders. From 26 to 52 weeks, 8 adverse effects (AE), including 1 serious AE (cerebrovascular accident) were reported in 5 subjects. None of the new adverse events were thought to be device related. CONCLUSION: This open-label study suggests persistent benefits and safety of iPAAG through 52 weeks after a single injection. TRIAL REGISTRATION: Clinicaltrials.gov NCT04179552.

The effect of graded activity and pain education after lumbar spinal fusion on sedentary behavior 3 and 12 months post-surgery: a randomized controlled trial.

OBJECTIVES: To examine the effect of an early post-surgical intervention consisting of graded activity and pain education (GAPE) in patients with chronic low back pain (CLBP) undergoing lumbar spinal fusion (LSF) on sedentary behaviour, disability, pain, fear of movement, self-efficacy for exercise and health-related quality of life (HRQoL) at three-, six- and 12 months follow-up. DESIGN: A parallel-group, observer-blinded randomized controlled trial. SETTING: Department of Occupational- and Physiotherapy and the Centre for Rheumatology and Spine Diseases, Rigshospitalet, Denmark. PARTICIPANTS: In total, 144 participants undergoing an LSF for CLBP were randomly assigned to an intervention- or a control group. INTERVENTION: The intervention group received nine sessions of GAPE, based on principles of operant conditioning. OUTCOME: The primary outcome was reduction in time spent in sedentary behaviour, measured by an accelerometer at three months. The secondary outcomes were reduction in time spent in sedentary behaviour at 12 months and changes from baseline to three-, six- and 12 months on disability, pain, fear of movement, self-efficacy for exercise and HRQoL. RESULTS: No difference in changes in sedentary behaviour between groups was found three months after surgery. At 12 months after surgery there was a significant difference between groups (mean difference: -25.4 minutes/day (95% CI -49.1 to -1.7)) in favour of the intervention group. CONCLUSION: Compared with usual care, GAPE had no effect on short-term changes in sedentary behaviour but GAPE had a statistically, but possibly not clinically effect on sedentary behaviour 12 months after LSF. Further, the behavioural intervention was safe to perform.

Comparative effectiveness of different placebos and comparator groups for hand osteoarthritis exploring the impact of contextual factors: A systematic review and meta-analysis of randomised trials.

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.

Polyacrylamide gel versus hyaluronic acid for the treatment of knee osteoarthritis: a randomised controlled study.

OBJECTIVES: To assess non-inferiority of intra-articular injectable polyacrylamide hydrogel (iPAAG) to hyaluronic acid (HA) on symptomatic benefit in individuals with knee osteoarthritis (OA). METHODS: This randomised, controlled, multi-centre trial recruited adults with symptomatic and radiographic knee OA from 3 clinical rheumatology sites in Denmark; two private clinics and one public hospital department. Participants were randomised 1:1 to receive a single intra-articular 6 mL injection of either HA or iPAAG on an outpatient basis. Primary outcome was change from baseline in WOMAC pain subscale after 26 weeks. Secondary outcomes were changes from baseline in WOMAC stiffness and physical function subscales, patients' global assessment of disease impact, EuroQoL-5D-5L, and proportion of positive OMERACT-OARSI responders after 26 and 52 weeks. RESULTS: 239 adults were randomised: 120 to HA and 119 to iPAAG. For the primary outcome, the least squares mean changes in WOMAC pain were -14.8 (95% CI: -18.0 to -11.7) for HA and -18.5 (95% CI: -21.7 to -15.4) for iPAAG; group difference: 3.7 (95% CI: -0.7 to 8.1). The lower boundary of the 95% CI respected the pre-specified non-inferiority margin of 9 WOMAC pain points. No statistically significant differences were observed for the secondary outcomes. For HA, 9 participants (7.6%) reported 13 adverse device effects (ADEs). For iPAAG, 35 participants (28.9%) reported 41 ADEs. All ADEs were mild/moderate, with no serious ADEs reported. CONCLUSIONS: iPAAG was found to be as effective and safe as HA for treatment of knee OA symptoms for at least 1 year after a single injection.

Exercise for knee osteoarthritis pain: Association or causation?

Exercise is universally recommended as a primary strategy for the management of knee osteoarthritis (OA) pain. The recommendations are based on results from more than 100 randomized controlled trials (RCTs) that compare exercise to no-attention control groups. However, due to the inherent difficulties with adequate placebo control, participant blinding and the use of patient-reported outcomes, the existing RCT evidence is imperfect. To better understand the evidence used to support a causal relationship between exercise and knee OA pain relief, we examined the existing evidence through the Bradford Hill considerations for causation. The Bradford Hill considerations, first proposed in 1965 by Sir Austin Bradford Hill, provide a framework for assessment of possible causal relationships. There are 9 considerations by which the evidence is reviewed: Strength of association, Consistency, Specificity, Temporality, Biological Gradient (Dose-Response), Plausibility, Coherence, Experiment, and Analogy. Viewing the evidence from these 9 viewpoints did neither bring forward indisputable evidence for nor against the causal relationship between exercise and improved knee OA pain. Rather, we conclude that the current evidence is not sufficient to support claims about (lack of) causality. With our review, we hope to advance the continued global conversation about how to improve the evidence-based management of patients with knee OA.

Weight Loss for Patients With Gout and Concomitant Obesity: A Proof-of-Concept Randomized Trial.

OBJECTIVE: Despite scarce evidence, guidelines recommend weight loss as a management strategy for patients with gout. We investigated the effect of an intensive dietary intervention on body weight and clinical measures of gout severity in individuals with obesity and gout. METHODS: We conducted a 16-week randomized nonmasked parallel-group trial in Denmark, randomly assigning (one-to-one) individuals with obesity and gout to a low-energy diet or a control diet. The primary outcome was change in body weight. Key secondary outcomes were changes in serum urate (SU) level and visual analog scale-assessed pain and fatigue. RESULTS: Between December 1, 2018, and June 1, 2019, 61 participants were included in the intention-to-treat population and randomly assigned to the intensive diet group (n = 29) or control diet group (n = 32). Participants had a mean age of 60.3 (SD 9.9) years and mean body mass index of 35.6 (SD 5.0), and 59 (97%) were men. After 16 weeks, there was a significant difference in change in body weight between the diet and control groups (-15.4 vs -7.7 kg; difference -7.7 kg [95% confidence interval -10.7 to -4.7], P < 0.001). Despite results being potentially in favor of a low-energy diet, we could not confirm differences in SU level changes and fatigue between groups. No differences in pain and gout flares were observed between groups. No serious adverse events or deaths occurred during the trial. CONCLUSION: An intensive dietary intervention was safe and effectively lowered body weight in people with obesity and gout, but the weight loss did not directly translate into effects on SU level, fatigue, and pain.

Sensitivity of simulated knee joint mechanics to selected human and bovine fibril-reinforced poroelastic material properties.

Fibril-reinforced poroviscoelastic material models are considered state-of-the-art in modeling articular cartilage biomechanics. Yet, cartilage material parameters are often based on bovine tissue properties in computational knee joint models, although bovine properties are distinctly different from those of humans. Thus, we aimed to investigate how cartilage mechanical responses are affected in the knee joint model during walking when fibril-reinforced poroviscoelastic properties of cartilage are based on human data instead of bovine. We constructed a finite element knee joint model in which tibial and femoral cartilages were modeled as fibril-reinforced poroviscoelastic material using either human or bovine data. Joint loading was based on subject-specific gait data. The resulting mechanical responses of knee cartilage were compared between the knee joint models with human or bovine fibril-reinforced poroviscoelastic cartilage properties. Furthermore, we conducted a sensitivity analysis to determine which fibril-reinforced poroviscoelastic material parameters have the greatest impact on cartilage mechanical responses in the knee joint during walking. In general, bovine cartilage properties yielded greater maximum principal stresses and fluid pressures (both up to 30%) when compared to the human cartilage properties during the loading response in both femoral and tibial cartilage sites. Cartilage mechanical responses were very sensitive to the collagen fibril-related material parameter variations during walking while they were unresponsive to proteoglycan matrix or fluid flow-related material parameter variations. Taken together, human cartilage material properties should be accounted for when the goal is to compare absolute mechanical responses of knee joint cartilage as bovine material parameters lead to substantially different cartilage mechanical responses.

Effect of research participation versus usual clinical care in patients with rheumatic and musculoskeletal disorders: a prospective cohort study.

OBJECTIVE: To compare illness perception (IP), pain, functional level and health-related quality of life (HR-QoL) between patients with musculoskeletal pain who participate versus those who do not participate in clinical research projects. METHODS: Data were collected between 1 January 2019 and 31 December 2021 in patients visiting the Outpatient Osteoarthritis Clinic at Frederiksberg Hospital, Copenhagen, as part of either clinical research or regular treatment. Questionnaires were collected at baseline and after 10-18 months. Major outcome measure was the change from baseline to follow-up in the Brief Pain Inventory - Short Form (BPI-SF) item 'Average pain'. Secondary outcome measures included The Brief Illness Perception Questionnaire (B-IPQ), measured only at baseline, the EuroQol (EQ-5D-3L), the Health Assessment Questionnaire Disability Index and PainDETECT. RESULTS: 1495 patients were included with 358 (24%) categorised as research participants (exposed) and 1137 (76%) being non-participants (unexposed). The baseline B-IPQ item scores were generally more favourable in the exposed group with statistically significant standardised differences (SD) of 0.2-0.3. Similarly, an SD of 0.3 on the EQ-5D-3L score indicated a better HR-QoL in the exposed group. At follow-up, 24% in the exposed group and 27% in the unexposed group, completed the questionnaires. The mean BPI-sf Average pain between-group difference was: -0.01 points (95% CI: -0.6 to 0.6). Similar clinically irrelevant differences were seen in the other outcomes. CONCLUSIONS: Among musculoskeletal pain patients, research participants report more positive IP and better HR-QoL than non-participants. No additional effect of research participation was found in any outcome over time. TRIAL REGISTRATION NUMBER: NCT03785561.

Comparative effectiveness of pharmacological interventions for hand osteoarthritis: a systematic review and network meta-analysis of randomised trials.

OBJECTIVE: To explore the comparative effectiveness of pharmacological interventions for hand osteoarthritis (OA). METHODS: We systematically searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception until 26 December 2021, for randomised trials of pharmacological interventions for people with hand OA. Two reviewers independently extracted study data and assessed the risk of bias. We calculated the effect sizes for pain (standardised mean differences) using Bayesian random effects models for network meta-analysis (NMA) and pairwise meta-analysis. Based on a pre-specified protocol, we prospectively registered the study at PROSPERO, CRD42021215393. RESULTS: We included 72 trials with 7609 participants. 65 trials (n=5957) were eligible for the quantitative synthesis, investigating 29 pharmacological interventions. Oral non-steroidal anti-inflammatory drugs (NSAIDs) and oral glucocorticoids' NMA effect sizes were -0.18 (95% credible interval -0.36 to 0.02) and -0.54 (-0.83 to -0.24), respectively, compared with placebo, and the result was consistent when limiting evidence to the pairwise meta-analysis of trials without high risk of bias. Intra-articular hyaluronate, intra-articular glucocorticoids, hydroxychloroquine, and topical NSAIDs' NMA effect sizes were 0.22 (-0.08 to 0.51), 0.25 (0.00 to 0.51), -0.01 (-0.19 to 0.18), and -0.14 (-0.33 to 0.08), respectively, compared with placebo. Oral NSAIDs were inferior to oral glucocorticoids with an NMA effect size of 0.36 (0.01 to 0.72). No intervention was superior to placebo when stratifying for thumb and finger OA. CONCLUSION: Oral NSAIDs and glucocorticoids are apparently effective pharmacological interventions in hand OA. Intra-articular therapies and topical NSAIDs were not superior to placebo.

Prognostic value of illness perception on changes in knee pain among elderly individuals: Two-year results from the Frederiksberg Cohort study.

Objective: To investigate the prognostic value of illness perception (IP) on knee pain, quality of life (QoL) and functional level in elderly individuals reporting knee pain. Design: A prospective cohort study of 1552 elderly with knee pain comparing two previously established clusters based on the Brief Illness Perception questionnaire. Cluster 1 ("Concerned optimists" [hypothesized unfavorable profile]; n â€‹= â€‹642) perceived their knee pain as a greater threat to them than Cluster 2 ("Unconcerned confident" [hypothesized favorable profile]; n â€‹= â€‹910). Primary outcome was the change from baseline to year 2 in the KOOS Pain subscale. Secondary outcomes were changes from baseline in quality of life (EuroQol-5 Domain and EQ VAS) and in the KOOS subscales Symptom, Activities of Daily Living, Knee-related QoL and Sports and recreation. Analyses were done on the original Intention-To-Survey (ITS) population, using repeated measures mixed linear models. Results: Among the ITS population, 841 (54%) responded to the 2-year survey. There was a statistically significant but clinically irrelevant cluster difference in the 2-year change from baseline in KOOS pain (mean difference: 6.0 KOOS points [95% CI: 7.3 to -4.7]) explained by a minor improvement in Cluster 1: (6.2 points) and no changes in Cluster 2: (0.2 points). Comparable results were found across the secondary outcomes. Clinically irrelevant cluster changes in IP were seen. Conclusion: In a cohort of people with knee pain, IP phenotype (i.e., Clusters) were of no prognostic value for the 2-year changes in pain, function, and QoL. Targeting IP may not be relevant in this patient population. Trial registration number and date of registration: The Frederiksberg Cohort study was pre-registered at clinicaltrials.gov (NCT03472300) on March 21, 2018.

Effectiveness of an individualised occupational therapy intervention programme (ABLE) using adaptational strategies on activities of daily living among persons with chronic conditions: A randomised controlled trial (RCT).

OBJECTIVE: Compare the effectiveness of a problem-solving, individualised, home-based occupational therapy intervention (ABLE 2.0), to usual occupational therapy, on activities of daily living (ADL) ability in persons with chronic conditions. DESIGN: A single-centre, double-blinded, randomised controlled trial with 10- and 26-week follow-up. SETTING: A Danish municipality. SUBJECTS: Persons with chronic conditions experiencing problems performing ADL tasks (n = 80). INTERVENTIONS: ABLE 2.0 was compared with usual occupational therapy. MAIN MEASURES: Coprimary outcomes were self-reported ADL ability (ADL-Interview Performance) and observed ADL motor ability (Assessment of Motor and Process Skills) at Week 10. Secondary outcomes were self-reported ADL ability (ADL-Interview Performance) and observed ADL motor ability (Assessment of Motor and Process Skills) at Week 26, and perceived satisfaction with ADL ability (ADL-Interview Satisfaction) and observed ADL process ability (Assessment of Motor and Process Skills) at Weeks 10 and 26. RESULTS: In total, 78 persons were randomly assigned: 40 to usual occupational therapy and 38 to ABLE 2.0. No statistically significant nor clinically relevant difference between group mean changes in primary outcomes was identified from baseline to Week 10 (ADL-Interview Performance [-0.16; 95% CI: -0.38 to 0.06] and Assessment of Motor and Process Skills ADL motor ability [-0.1; 95% CI: -0.3 to 0.1]). At Week 26, a statistically significant and clinically relevant difference was found in Assessment of Motor and Process Skills ADL motor ability (LS mean change: -0.3; 95% CI: -0.5 to -0.1) between groups. CONCLUSION: ABLE 2.0 was effective in improving observed ADL motor ability at 26 weeks.

Effect of High-Intensity Interval Training on Inhaled Corticosteroid Dose in Asthma Patients: A Randomized Controlled Trial.

BACKGROUND: Inhaled corticosteroids (ICS) are the cornerstone of asthma treatment. However, ICS has side effects, and dose reduction is recommended when possible. Physical exercise improves asthma control, but it is unknown whether it reduces the reliance on ICS. OBJECTIVE: To assess whether supervised high-intensity interval training reduces the need for ICS in untrained asthma patients. METHODS: An assessor-blinded single-center randomized controlled trial, Copenhagen, Denmark. One hundred fifty untrained ICS-treated adults with symptomatic asthma were randomly assigned (2:1) to 6 months of supervised exercise 3 times weekly or a lifestyle as usual control group. Every second month, a clinical algorithm based on symptom control was applied in both groups to adjust ICS dose. Primary outcome was the proportion who had their ICS dose reduced by 25% or more after 6 months. Secondary outcomes included actual ICS dosage in micrograms per day. RESULTS: Between October 2017 and December 2019, 102 patients were allocated to exercise intervention (86% completed) and 48 to the control (85% completed). At the 6-month visit, 63% versus 50% met the primary outcome in the exercise and control groups, respectively (adjusted risk difference 9.6% [95% CI -3.8 to 18.8]; P = .15). Daily ICS dose was reduced in favor of the exercise group, with a mean difference of -234 µg (95% CI -391 to -77; P = .0037), corresponding to a 24% reduction from baseline. This effect was sustained at 12 months. The intervention was safe and well tolerated. CONCLUSIONS: Six months of regular exercise results in reduction in daily ICS dose without compromising asthma control.

Quadriceps or hip exercises for patellofemoral pain? A randomised controlled equivalence trial.

OBJECTIVE: To assess effectiveness equivalence between two commonly prescribed 12-week exercise programmes targeting either the quadriceps or the hip muscles in patients with patellofemoral pain (PFP). METHODS: This randomised controlled equivalence trial included patients with a clinical diagnosis of PFP. Participants were randomly assigned to either a 12-week quadriceps-focused exercise (QE) or a hip-focused exercise (HE) programme. The primary outcome was the change in Anterior Knee Pain Scale (AKPS) (0-100) from baseline to 12-week follow-up. Prespecified equivalence margins of ±8 points on the AKPS were chosen to demonstrate comparable effectiveness. Key secondary outcomes were the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire pain, physical function and knee-related quality of life subscales. RESULTS: 200 participants underwent randomisation; 100 assigned to QE and 100 to HE (mean age 27.2 years (SD 6.4); 69% women). The least squares mean changes in AKPS (primary outcome) were 7.6 for QE and 7.0 for HE (difference 0.6 points, 95% CI -2.0 to 3.2; test for equivalence p<0.0001), although neither programme surpassed the minimal clinically important change threshold. None of the group differences in key secondary outcomes exceeded predefined equivalence margins. CONCLUSION: The 12-week QE and HE protocols provided equivalent improvements in symptoms and function for patients with PFP. TRIAL REGISTRATION NUMBER: NCT03069547.

Physiotherapists' prognosis of 1-year outcome after lumbar spinal fusion - A prospective cohort study.

BACKGROUND: Physiotherapists (PTs) have an essential role in the facilitation of patients' mobilization after lumbar spinal fusion (LSF). The aim of this study is to investigate whether PTs can predict one-year post-surgery outcome based on their first meeting with the patient immediately after LSF. METHOD: A prospective cohort study with one-year follow-up was conducted. In the first days after surgery, the PTs from hospital wards were asked to predict the patients' overall LSF outcome one year after surgery. One year after surgery, the patients received a questionnaire including the Oswestry Disability Index (ODI), visual analogue scales (VAS) for leg and back pain, quality of life survey (EQ-5D-3 L), global perceived effect (GPA), and satisfaction with surgery outcome (SSO). Univariate and logistic regression were used to calculate the associations between the prognosis and predictive values. RESULTS: The study included 170 patients. The analyses showed a significant association between the PTs' prognosis and the primary outcome ODI (p < .01), VAS leg and back, EQ-5D-3 L, and GPE one-year post-surgery (p ≤ .04). However, the predictive value of the PTs' prognosis was low (R2 ≤ 0.09). There was no significant association between the PTs' prognosis and the patients' SSO (p = .17; R2 = 0.01). CONCLUSION: There were significant associations between the PTs' prognosis and disability, pain, health-related quality of life and global perceived effect one-year post-surgery, although the associations had low predictive values. There was no significant association between the PTs' prognosis and patients' SSO after one year. The PTs' prognosis should not be used as a single component in further rehabilitation planning.

Effects of a 12-week supervised resistance training program, combined with home-based physical activity, on physical fitness and quality of life in female breast cancer survivors: the EFICAN randomized controlled trial.

PURPOSE: This study assessed the effects of 12-week supervised resistance training combined with home-based physical activity on physical fitness, cancer-related fatigue, depressive symptoms, health-related quality of life (HRQoL), and life satisfaction in female breast cancer survivors. METHODS: A parallel-group, outcome assessor-blinded, randomized controlled trial included 60 female breast cancer survivors who had completed their core treatments within the previous 10 years. Through computer-generated simple randomization, participants were assigned to resistance training (RTG; two sessions/week for 12 weeks plus instructions to undertake ≥ 10,000 steps/d) or control (CG; ≥ 10,000 steps/d only). Outcomes were evaluated at baseline and week 12. Muscular strength was assessed with electromechanical dynamometry. A standardized full-body muscular strength score was the primary outcome. Secondary outcomes included cardiorespiratory fitness, shoulder mobility, cancer-related fatigue, depressive symptoms, HRQoL, and life satisfaction. RESULTS: Thirty-two participants were assigned to RTG (29 achieved ≥ 75% attendance) and 28 to CG (all completed the trial). Intention-to-treat analyses revealed that the standardized full-body muscular strength score increased significantly in the RTG compared to the CG (0.718; 95% CI 0.361-1.074, P < 0.001, Cohen's d = 1.04). This increase was consistent for the standardized scores of upper-body (0.727; 95% CI 0.294-1.160, P = 0.001, d = 0.87) and lower-body (0.709; 95% CI 0.324-1.094, P = 0.001, d = 0.96) strength. There was no effect on cardiorespiratory fitness, shoulder flexion, cancer-related fatigue, depressive symptoms, HRQoL, or life satisfaction. The sensitivity analyses confirmed these results. CONCLUSION: and implication for cancer survivors. In female breast cancer survivors who had completed their core treatments within the past 10 years, adding two weekly sessions of supervised resistance training to a prescription of home-based physical activity for 12 weeks produced a large increase in upper-, lower-, and full-body muscular strength, while other fitness components and patient-reported outcomes did not improve. TRIAL REGISTRATION NUMBER: ISRCTN14601208.

Hemodynamic Response in Ascending Aorta Surgery Patients during Moderate Intensity Resistance Training.

Background: In patients undergoing ascending aortic surgery (AAS), postsurgical physical exercise with a safe and effective exercise prescription is recommended. Resistance training is associated with blood pressure (BP) elevations that may increase the risk of new aortic dissection or rupture. However, the acute hemodynamic response to resistance training for this patient group is unknown. Aim: The aim of this study was to investigate peak systolic BP (SBP) increases in AAS patients during moderate intensity resistance training. Methods: SBP was measured continuously beat-to-beat with a noninvasive method during three sets of leg presses at moderate intensity. A 15-repetition maximum strength test was performed to estimate the maximal amount of resistance a participant could manage 15 times consecutively (equivalent to approximately 60-65% of their maximum strength). Results: The study had 48 participants in total, i.e., 24 cases and 24 controls. Both groups consisted of 10 females (42%) and 14 males (58%). The case group had a mean age of 60.0 (SD ± 11.9) years and a mean of 16.3 months since surgery (minimum 4.4 and maximum 39.6 months). 22 of the 24 cases received antihypertensive medication. The median baseline BP was 119/74 mmHg among cases and 120/73 mmHg among controls. During the first set of leg presses, the median peak SBP was 152 mmHg, in the second set 154 mmHg, and in the third set 165 mmHg. Corresponding values in controls were 170 mmHg, 181 mmHg, and 179 mmHg. The highest peak SBP registered in an AAS patient was 190 mmHg and in any healthy control was 287 mmHg. Conclusion: The findings indicate that AAS patients in control of their BP have the endurance to perform 3 sets of resistance training at moderate intensity as their SBP increases with a maximum of 39% from the baseline compared to the 51% increase in the control group.

Colchicine twice a day for hand osteoarthritis (COLOR): a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Colchicine has been suggested for osteoarthritis treatment, but evidence is contradictory. We aimed to investigate colchicine's efficacy and safety compared with placebo in people with hand osteoarthritis. METHODS: In this single-centre, double-blind, randomised, placebo-controlled trial we recruited adults with symptomatic hand osteoarthritis and finger pain of at least 40 mm on a 100 mm visual analogue scale from an outpatient clinic in Denmark. The hand with the most severe finger pain at inclusion was the target hand. Participants were randomly assigned (1:1) to 0·5 mg colchicine or placebo taken orally twice a day for 12 weeks, stratified by BMI (≥30 kg/m2), sex, and age (≥75 years). Participants, outcome assessors, and data analysts were masked to treatment allocation. The primary endpoint was change from baseline to week 12 in target hand finger pain, assessed on a 100 mm visual analogue scale with a pre-specified minimal clinically important difference of 15 mm, in the intention-to-treat population. Safety was assessed at week 12 in the intention-to-treat population. The study was registered with ClinicalTrials.gov, NCT04601883, and with EudraCT, 2020-002803-20. FINDINGS: Between Jan 15, 2021, and March 3, 2022, 186 people were screened for eligibility, and 100 were randomly assigned to receive colchicine (n=50) or placebo (n=50). Participants had a mean age of 70·9 (SD 7·5) years, 69 (69%) of 100 were women and 31 (31%) were men. All participants completed the study. The mean change from baseline to week 12 in finger pain were -13·9 mm (SE 2·8) in the colchicine group and -13·5 mm (2·8) in the placebo group, with a between-group difference (colchicine vs placebo) of -0·4 mm (95% CI -7·6 to 6·7; p=0·90). In the colchicine group, there were 76 adverse events in 36 (72%) of 50 participants and one serious adverse advent (migraine attack leading to hospital admission). In the placebo group, there were 42 adverse events in 22 (44%) of 50 participants and two serious adverse events (cholecystitis and elevated alanine aminotransferase concentrations, in the same patient). INTERPRETATION: In people with painful hand osteoarthritis, treatment with 0·5 mg of colchicine twice day for 12 weeks did not effectively relieve pain, and treatment with colchicine was associated with more adverse events. FUNDING: The Oak Foundation, IMK Almene Fond, Minister Erna Hamilton's Scholarship for Science and Art, AP Moller and Wife Chastine McKinney Moller's Foundation for Medical Science Advancement, The Danish Medical Association, the Velux Foundation, Aase and Ejnar Danielsen's Foundation, and Director Emil C Hertz and Wife Inger Hertz's foundation.

Changes in physical activity during a one-year weight loss trial with liraglutide vs placebo in participants with knee osteoarthritis: Secondary analyses of a randomised controlled trial.

Objective: To assess if a change in physical activity occurred after a one-year weight loss period on either liraglutide or placebo in patients with knee osteoarthritis (OA) and overweight. Method: This is secondary analysis of a one-year weight loss trial, with participants randomised (1:1) to either liraglutide 3 â€‹mg/day or placebo. The main outcome was change in physical activity (min/day) after one year assessed by accelerometer. Physical function was assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS), function subscale with 100 indicating no disability and 0 indicating extreme disability. Analyses were done on the modified intention to treat population defined as complete baseline accelerometer data. Results: A total of 135 participants were analysed (66 liraglutide; 69 placebo). Daily physical activity time did not change in either group (liraglutide: 15.8 â€‹min/day; placebo: 14.2 â€‹min/day; mean difference 1.6 â€‹min/day (95%CI -16 to 19; P â€‹= â€‹0.90)). The liraglutide group lost -4.1 â€‹kg more than placebo (95% CI -6.0 to -2.1; P â€‹< â€‹0.0001) and improved in KOOS function 3.8 points more than placebo (95% CI 0.9 to 6.7; P â€‹= â€‹0.01). Conclusion: Despite better outcomes on body weight and self-reported physical functioning liraglutide did not induce changes in physical activity over one year in individuals with knee OA.