Therapeutic exercise for knee osteoarthritis is recommended globally, based on more than 100 randomised, controlled trials documenting beneficial effects on pain and function. There are adverse effects of exercise and symptom exacerbations may occur in the first 4-6 weeks of an exercise programme, but will most often decline with time. If pain and function do not improve after a structured exercise program, other treatments must be considered. The effects of exercise decline over time, if regular exercise is not implemented in the daily life of the patient.

OBJECTIVE: Randomized controlled trials (RCTs) are considered the gold standard in clinical research due to credible causality. Their results, however, may not be generalizable to real-world populations. While glucocorticoids (GCs) remain a mainstay of rheumatoid arthritis (RA) treatment, it is unclear whether the results of GC-RCTs are generalizable to current real-world RA patients.

METHODS: MEDLINE was searched for RCTs and, as comparators, cohort studies (CSs) in RA evaluating systemic GCs. Random-effects meta-analyses were performed for descriptive baseline characteristics (including general demographics, comorbidities, and disease activity) that have been shown to be able to modify the benefit-risk-ratio of various RA therapeutics. These meta-analyses were stratified by study type (RCT and CS). Stratified estimates were subsequently compared. Further sensitivity analyses were performed stratifying by disease duration.

RESULTS: 56 RCTs (7053 participants) and 10 CSs (14,688 participants) were included. 12 characteristics were reported frequently enough to allow for comparative analysis. In 10/12 characteristics (83%), RCT estimates did not appear to differ from CS estimates. However, RCT participants were younger (-4.7 years [95% CI -7.2 to -2.1]; p < 0.001) and had higher erythrocyte sedimentation rates (11.8 mm/h [5.7 to 17.8]; p < 0.001) than CS participants. Comorbidities could not be assessed due to insufficient reporting.

CONCLUSION: Our findings suggest that evidence from GC trials in RA is of acceptable generalizability to current real-world patients - especially compared to findings from biologic agents in RA. However, RCT participants were younger than real-world patients, potentially limiting the generalizability of trial results to elderly patients.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42019134675).

BACKGROUND: Myocardial injury after non-cardiac surgery occurs in a high number of patients, resulting in increased mortality in the post-operative period. The use of high inspiratory oxygen concentrations may cause hyperoxia, which is associated with impairment of coronary blood flow. Furthermore, the surgical stress response increases reactive oxygen species, which is involved in several perioperative complications including myocardial injury and death. Avoidance of hyperoxia and substitution of reactive oxygen species scavengers may be beneficial. Our primary objective is to examine the effect of oxygen and added antioxidants for prevention of myocardial injury assessed by area under the curve for troponin measurements during the first three post-operative days.

METHODS: The VIXIE trial (VitamIn and oXygen Interventions and cardiovascular Events) is an investigator-initiated, blinded, 2 × 2 factorial multicentre clinical trial. We include 600 patients with cardiovascular risk factors undergoing major non-cardiac surgery. Participants are randomised to an inspiratory oxygen fraction of 0.80 or 0.30 during and for 2 hours after surgery and either an intravenous bolus of vitamin C and an infusion of N-acetylcysteine or matching placebo of both. The primary outcome is the area under the curve for high-sensitive cardiac troponin release during the first three post-operative days as a marker of the extent of myocardial injury. Secondary outcomes are mortality, non-fatal myocardial infarction and non-fatal serious adverse events within 30 days.

PERSPECTIVE: The current trial will provide further evidence for clinicians on optimal administration of perioperative oxygen in surgical patients with cardiovascular risks and the clinical effects of two common antioxidants.