Stepped wedge and cluster randomised crossover trials are examples of cluster randomised designs conducted over multiple time periods that are being used with increasing frequency in health research. ...Recent systematic reviews of both of these designs indicate that the within-cluster correlation is typically taken account of in the analysis of data using a random intercept mixed model, implying a constant correlation between any two individuals in the same cluster no matter how far apart in time they are measured: within-period and between-period intra-cluster correlations are assumed to be identical. Recently proposed extensions allow the within- and between-period intra-cluster correlations to differ, although these methods require that all between-period intra-cluster correlations are identical, which may not be appropriate in all situations. Motivated by a proposed intensive care cluster randomised trial, we propose an alternative correlation structure for repeated cross-sectional multiple-period cluster randomised trials in which the between-period intra-cluster correlation is allowed to decay depending on the distance between measurements. We present results for the variance of treatment effect estimators for varying amounts of decay, investigating the consequences of the variation in decay on sample size planning for stepped wedge, cluster crossover and multiple-period parallel-arm cluster randomised trials. We also investigate the impact of assuming constant between-period intra-cluster correlations instead of decaying between-period intra-cluster correlations. Our results indicate that in certain design configurations, including the one corresponding to the proposed trial, a correlation decay can have an important impact on variances of treatment effect estimators, and hence on sample size and power. An R Shiny app allows readers to interactively explore the impact of correlation decay.
Summary Objective To investigate relationships between external knee adduction moment parameters (KAM) and osteoarthritis (OA) symptoms according to disease severity. Design 164 participants with ...symptomatic medial knee OA were included. Radiographic severity was graded by (1) Kellgren & Lawrence (KL) scale (Grade 2, n = 49; Grade, n = 52; Grade 4, n = 63) and; (2) medial tibiofemoral joint space narrowing (JSN) (Grade 1, n = 47; Grade 2, n = 50; Grade 3, n = 67). KAM-related parameters (peak KAM, KAM impulse and cumulative load) were determined from three-dimensional gait analysis and pedometry. Cumulative load was determined by multiplying KAM impulse by the average number of steps/day recorded over at least 5 days. Symptoms were assessed via numeric rating scale ((NRS), pain) and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index (pain and physical function). Relationships between KAM parameters (independent variables) and symptoms (dependent variables) were evaluated by radiographic severity using linear models, adjusting for covariates. Results In mild disease (either KL Grade 2 or JSN Grade 1), there were no associations between KAM and symptoms. In moderate disease of KL Grade 3, higher KAM impulse was associated with greater WOMAC pain. In severe disease (KL Grade 4), higher KAM impulse was associated with less WOMAC pain (KL Grade 4), while higher peak KAM was associated with better function (KL Grade 4). Higher cumulative knee adduction load was associated with less pain on both NRS and WOMAC (JSN Grade 3) as well as better function (both JSN Grade 3 and KL Grade 4). Conclusions Relationships between KAM-related parameters and symptoms differ according to underlying radiographic OA severity.
To determine if an increase in knee extensor strength mediates the effect of a 12-week knee extensor strength training program on pain and physical function improvement in people with knee ...osteoarthritis (OA).
Secondary analysis from a randomised controlled trial comparing the effects of a 12-week knee extensor strengthening exercise program to a control group with no intervention.
Data from participants with complete data (n = 97) enrolled in a previous clinical trial were analysed. Baseline and 12-week follow-up assessments included peak isometric knee extensor strength, pain and physical function. Peak knee extensor strength (Nm/kg) was assessed on an isokinetic dynamometer and subscales of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index were used to assess pain and physical function. Twelve-week change in pain and physical function were regressed separately, on 12-week change in knee extensor strength and group allocation. Covariates included baseline pain or physical function as appropriate, and baseline knee extensor strength, age, sex and knee alignment (stratification variable).
Improved knee extensor strength mediated the effect of the strengthening program on both pain relief (mediated effect size = 0.69, 95% confidence intervals (CI) 0.05–1.33, P = 0.03), and improved physical function (mediated effect size = 1.86, 95% CI 0.08–3.64, P = 0.04), at 12 weeks.
Increased knee extensor strength partially mediates the effect of a knee extensor strength training program on pain and physical function improvement in people with knee OA.
To investigate the presence of different trajectories of self-reported adherence to home exercise programs among people with knee osteoarthritis (OA), and to compare baseline characteristics across ...identified groups.
Pooled analysis of data from three randomised controlled trials involving exercise interventions for people aged ≥50 years with clinical knee OA (n = 341). Exercise adherence was self-reported on an 11-point numerical rating scale (NRS; 0 = not at all-10 = completely as instructed). Latent class growth analysis was used to identify distinct trajectories of adherence, at intervals from 12 to 78 weeks from baseline. Baseline characteristics of these groups were compared using chi-squared tests, one-way analysis of variance (ANOVA) and Kruskal Wallis tests where appropriate.
Three distinct adherence trajectories were identified: a “Rapidly declining adherence” group (n = 157, 47.4%) whose adherence was 7.7 ± 1.6 (/10) at 12 weeks, declined to 4.2 ± 2.2 by 22 weeks and remained low thereafter; a “Gradually declining adherence” group (n = 153, 45.1%) whose adherence declined from 8.5 ± 1.5 to 7.8 ± 1.5 over the same period, and continued to decline slowly, and a “Low adherence” group (n = 21, 6.3%) whose adherence was 2.2 ± 1.4 at 12 weeks and remained low. At baseline the “Rapidly declining adherence” group reported significantly lower Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (mean difference (95% Confidence Interval (CI)) −0.8 (−1.4, −0.2)) and better WOMAC function compared to the “Gradually declining adherence” group (−3.1 (−5.2, −1.1)).
Three trajectories of self-reported adherence to home exercises were found among people with knee OA. Findings highlight the need for close monitoring of adherence from initiation of a home exercise program in order to identify and intervene when low or rapidly declining adherence is identified.
Different exercise types may yield different outcomes in osteoarthritis (OA) subgroups. The objective was to directly compare effectiveness of two exercise programs for people with medial knee OA and ...co-morbid obesity.
We performed a participant- and assessor-blinded randomized controlled trial. 128 people ≥50 years with medial knee OA and body mass index ≥30 kg/m2 were recruited from the community. Interventions were home-based non-weight bearing (NWB) quadriceps strengthening or weight bearing (WB) functional exercise for 12 weeks.
Primary outcomes were change in overall knee pain (numeric rating scale, range 0–10) and difficulty with physical function (Western Ontario and McMaster Universities Osteoarthritis Index, 0–68) over 12 weeks. Secondary outcomes included other pain measures, physical function, quality-of-life, global changes, physical performance, and lower-limb muscle strength.
123 (96%) participants were retained. There was no evidence of a between-group difference in change in pain (mean difference 0.73 units (95% confidence intervals (0.05,1.50)) or function (2.80 units (−1.17,6.76)), with both groups reporting improvements. For secondary outcomes, the WB group had greater improvement in quality-of-life (−0.043 units (−0.085,-0.001)) and more participants reporting global improvement (overall: relative risk 1.40 (0.98,2.01); pain 1.47 (0.97,2.24); function 1.43 (1.04,1.98). Although adverse events were minor, more NWB group participants reported ≥1 adverse event (26/66 (39%) vs 14/62 (23%), p = 0.04).
Both exercise types similarly improved primary outcomes of pain and function and can be recommended for people with knee OA and obesity. WB exercise may be preferred given fewer adverse events and potential additional benefits on some secondary outcomes.
Prospectively registered (Australian New Zealand Clinical Trials Registry #12617001013358, 14/7/2017).
Abstract
The Aspirin in Reducing Events in the Elderly (ASPREE) Trial recruited 19,114 participants across Australia and the United States during 2010–2014. Participants were randomized to receive ...either 100 mg of aspirin daily or matching placebo, with disability-free survival as the primary outcome. During a median 4.7 years of follow-up, 37% of participants in the aspirin group permanently ceased taking their study medication and 10% commenced open-label aspirin use. In the placebo group, 35% and 11% ceased using study medication and commenced open-label aspirin use, respectively. In order to estimate compliance-adjusted effects of aspirin, we applied rank-preserving structural failure time models. The results for disability-free survival and most secondary endpoints were similar in intention-to-treat and compliance-adjusted analyses. For major hemorrhage, cancer mortality, and all-cause mortality, compliance-adjusted effects of aspirin indicated greater risks than were seen in intention-to-treat analyses. These findings were robust in a range of sensitivity analyses. In accordance with the original trial analyses, compliance-adjusted results showed an absence of benefit with aspirin for primary prevention in older people, along with an elevated risk of clinically significant bleeding.
Background. Service models for gastrointestinal endoscopy sedation must be safe, as endoscopy is the most common procedure performed under sedation in many countries. The aim of this prospective ...cohort study was to determine the patient risk profile, and incidence of and risk factors for significant unplanned events, in adult patients presenting for gastrointestinal endoscopy in a group of university-affiliated hospitals where most sedation is managed by anaesthetists.
Methods. Patients aged ≥18 yr presenting for elective and emergency gastrointestinal endoscopy under anaesthetist-managed sedation at nine hospitals affiliated with the University of Melbourne, Australia, were included. Outcomes included significant airway obstruction, hypoxia, hypotension and bradycardia; unplanned tracheal intubation; abandoned procedure; advanced life support; prolonged post-procedure stay; unplanned over-night admission and 30-day mortality.
Results. 2,132 patients were included. Fifty percent of patients were aged >60 yr, 50% had a BMI >27 kg m −2, 42% were ASA physical status III-V and 17% were emergency patients. The incidence of significant unplanned events was 23.0% (including significant hypotension 11.8%). Significant unplanned intraoperative events were associated with increasing age, BMI <18.5 kg m −2, ASA physical status III-V, colonoscopy and planned tracheal intubation. Thirty-day mortality was 1.2% (0.2% in electives and 6.0% in emergencies) and was associated with ASA physical status IV-V and emergency status.
Conclusions. Patients presenting for gastrointestinal endoscopy at a group of public university-affiliated hospitals where most sedation is managed by anaesthetists, had a high risk profile and a substantial incidence of significant unplanned intraoperative events and 30-day mortality.
Summary Objective To investigate whether foot and/or ankle symptoms increase the risk of developing (1) knee symptoms and (2) symptomatic radiographic knee osteoarthritis (OA). Design 1020 ...Osteoarthritis Initiative (OAI) participants who were at-risk of knee OA, but were without knee symptoms or radiographic knee OA, were investigated. Participants indicated the presence and laterality of foot/ankle symptoms at baseline. The main outcome was development of knee symptoms (pain, aching or stiffness in and around the knee on most days of the month for at least 1 month in the past year). A secondary outcome was development of symptomatic radiographic knee OA (symptoms plus Kellgren and Lawrence KL grade ≥2), over the subsequent 4 years. Associations between foot/ankle symptoms and study outcomes were assessed by logistic regression models. Results Foot/ankle symptoms in either or both feet significantly increased the odds of developing knee symptoms (adjusted odds ratio (OR) 1.55, 95% confidence interval (CI) 1.10 to 2.19), and developing symptomatic radiographic knee OA (adjusted OR 3.28, 95% CI 1.69 to 6.37). Based on laterality, contralateral foot/ankle symptoms were associated with developing both knee symptoms (adjusted OR 1.68, 95% CI 1.05 to 2.68) and symptomatic radiographic knee OA (adjusted OR 3.08, 95% CI 1.06 to 8.98), whilst bilateral foot/ankle symptoms were associated with developing symptomatic radiographic knee OA (adjusted OR 4.02, 95% CI 1.76 to 9.17). Conclusion In individuals at-risk of knee OA, the presence of contralateral foot/ankle symptoms in particular increases risk of developing both knee symptoms and symptomatic radiographic knee OA.
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