Compliance-Adjusted Estimates of Aspirin Effects Among Older Persons in the ASPREE Randomized Trial.

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.

What type of exercise is most effective for people with knee osteoarthritis and co-morbid obesity?: The TARGET randomized controlled trial.

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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). CONCLUSIONS: 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. REGISTRATION: Prospectively registered (Australian New Zealand Clinical Trials Registry #12617001013358, 14/7/2017).

A population-based epidemiological study of neuromyelitis optica spectrum disorder in Hungary.

BACKGROUND AND PURPOSE: The goal of this study was to determine the prevalence and incidence of neuromyelitis optica spectrum disorder (NMOSD) in Hungary based on the 2015 International Panel of NMO Diagnosis (IPND) criteria. METHODS: A retrospective population-based cohort study was conducted of 6.4 million Hungarians (age ≥ 16 years) between 1 January 2006 and 31 December 2016. Possible NMOSD patients were selected via multistage re-evaluation from multiple sources. Crude and sex- and serostatus-specific prevalence (per 100 000 persons) and incidence rates (per 1 000 000 person-years) from 2006 to 2015 were estimated and age-adjusted rates were determined. RESULTS: Of 2262 study candidates, 154 NMOSD patients (age ≥ 16 years) with onset until 31 December 2016 were identified based on 2015 IPND criteria. The prevalence analysis on 1 January 2016 included 123 NMOSD living cases, resulting in a prevalence of 1.91 [95% confidence interval (CI) 1.52-2.28] per 100 000 persons. The 101 incident cases emerging from the observed 76 394 288 person-years provided an incidence rate of 1.32 (95% CI 1.08-1.61) per 1 000 000 person-years. Age-adjusted prevalence was 1.87 (95% CI 1.56-2.23) per 100 000 persons and incidence was 1.20 (95% CI 0.98-1.46) per 1 000 000 person-years. CONCLUSIONS: In this first report of a large population-based epidemiological study from an Eastern European Caucasian population using robust case validation, a greater prevalence and incidence of NMOSD was found compared to previous large studies in Caucasian populations.

The influence of sex and pre-operative obesity on biomechanics two years after total knee arthroplasty: A longitudinal cohort study.

BACKGROUND: Sex and obesity may influence knee biomechanics associated with poor outcomes following primary total knee arthroplasty (TKA) however their long-term impact has not been investigated. RESEARCH QUESTION: Does sex and/or pre-operative obesity influence change in gait biomechanics from pre-TKA to two-years after TKA, and do knee biomechanics return to normal two-years after TKA? METHODS: In this longitudinal study, gait analysis was performed on 78 patients undergoing TKA for knee osteoarthritis prior to surgery (baseline), and on 66 (85 %) of these who returned at the two year follow-up. Gait biomechanics were also collected on a reference sample of 40 asymptomatic participants. Knee variables were analyzed according to time (pre- and post-TKA), sex (men and women), pre-operative obesity (obese vs non-obese), and group (TKA vs reference). Mixed linear regression models were used to examine the effects of TKA, obesity status, gender and all interactions. RESULTS: There were two-year reductions in peak knee frontal plane angle (mean difference -7.21°; 95% confidence intervals -9.37 to -5.05), peak knee adduction moment (KAM) (-17.64Nm; -23.04 to -12.24) and KAM impulse (-9.40Nm.s; -12.04 to -6.77) in males. These and other variables were unchanged in women. At two years, men exhibited a greater varus-valgus thrust excursion (4.9°; 2.7-7.2), and a lower peak knee frontal plane angle (-4.4°; -7.1 to -1.7) and peak KAM (-13.1Nm; -20.9 to -5.4), compared to the reference sample. Biomechanics at two years did not differ between pre-operative obesity subgroups, or between female TKA patients and the reference sample. SIGNIFICANCE: Changes in gait biomechanics two years after TKA are influenced by sex but not obesity. Men but not women showed altered knee biomechanics two years following TKR and compared to a reference sample. It is unknown whether these altered biomechanics in men impact longer term clinical outcomes and satisfaction following surgery.

Effect of cane use on bone marrow lesion volume in people with medial tibiofemoral knee osteoarthritis: randomized clinical trial.

OBJECTIVE: To evaluate effects of daily cane use for 3 months on medial tibiofemoral bone marrow lesion (BML) volumes in people with medial tibiofemoral osteoarthritis (OA). DESIGN: In this randomized controlled trial (RCT), 79 participants with medial tibiofemoral OA were randomized to either a cane group (using a cane whenever walking) or control group (not using any gait aid) for 3 months. The cane group received a single training session by a physiotherapist, using a biofeedback cane to teach optimal technique and body weight support and motor learning principles to facilitate retention of learning. The primary outcome was change in total medial tibiofemoral BML volume (per unit bone volume) measured from magnetic resonance imaging (MRI) at 3 months. Secondary outcomes were BML volumes (per unit bone volume) of the medial tibia and femur, and patient-reported outcomes of overall knee pain, knee pain on walking, physical function, perceived global symptom changes and health-related quality of life. MRI analyses were performed by a blinded assessor. RESULTS: Seventy-eight participants (99%) completed the primary outcome. Mean (standard deviation) daily cane use was 2.3 (1.7) hours over 3 months. No evidence of between-group differences was found for change in total medial tibiofemoral BML volume (mean difference: -0.0010 (95% confidence intervals: -0.0022, 0.0003)). Most secondary outcomes showed minimal differences between groups. CONCLUSION: Daily use of a cane during walking for 3 months aiming to reduce knee joint loading did not change medial tibiofemoral BML volumes compared to no use of gait aids. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ACTRN12614000909628).

Differences and mechanisms underpinning a change in the knee flexion moment while running in stability and neutral footwear among young females.

BACKGROUND: Higher peak external knee flexion moments (KFM) during running has been observed in healthy people wearing athletic footwear compared to barefoot, which may increase risk of knee pathologies such as patellofemoral pain. Currently, no studies have examined whether stability and neutral style athletic shoes influence the peak KFM differently, or explored the underlying biomechanical mechanisms by which footwear alters peak KFM in young females. METHODS: Lower limb biomechanics of sixty girls aged between 10 and 25 years old were collected while running in footwear (both stability and neutral) and barefoot. The external peak KFM, sagittal plane kinematics, sagittal plane knee ground reaction force (GRF) lever arm and sagittal plane resultant GRF magnitude were analysed by repeated measures Analysis of Variance. Linear mixed models were fit to identify predictors of a change in peak KFM, and to determine if the effects of these predictors differed between footwear conditions. RESULTS: The peak KFM was higher wearing both shoe styles compared to barefoot (p < 0.001), while no between-shoe differences were found (p > 0.05). Both shoes also increased kinematic variables at the hip, knee, and ankle (p < 0.05). When all these variables were entered into the mixed model, only a change in the knee-GRF lever arm was predictive of a change in peak KFM wearing shoes compared to barefoot (p < 0.001). CONCLUSION: These findings provide evidence that stability and neutral shoes increase peak KFM compared to barefoot, which is associated with a change in the knee-GRF lever arm rather than a change in lower limb kinematics. Future studies may consider manipulating footwear characteristics to reduce the knee-GRF lever arm in an effort to reduce peak KFM and the potential risk of patellofemoral pain.

Impact of non-uniform correlation structure on sample size and power in multiple-period cluster randomised trials.

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.

Correction to: Effectiveness of a new model of primary care management on knee pain and function in patients with knee osteoarthritis: Protocol for THE PARTNER STUDY.

After the publication of this protocol [1], our collaborator Prima Health solutions advised us of their intent to withdraw from the study.

Knee extensor strength gains mediate symptom improvement in knee osteoarthritis: secondary analysis of a randomised controlled trial.

OBJECTIVE: 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). DESIGN: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Effects of sex and obesity on gait biomechanics before and six months after total knee arthroplasty: A longitudinal cohort study.

BACKGROUND: Gait biomechanics, sex, and obesity can contribute to suboptimal outcomes from primary total knee arthroplasty. The aims of this study were to i) determine if sex and/or obesity influence the amount of change in gait biomechanics from pre-surgery to six months post-surgery and; ii) assess if gait returns to normal in men and women. METHODS: Three-dimensional gait analysis was performed on 43 patients undergoing primary total knee arthroplasty for knee osteoarthritis (pre- and six months post-operative) and 40 asymptomatic controls. Mixed linear regression models were fit to assess which factors influenced change in gait biomechanics within the arthroplasty cohort, and interaction terms were included to assess if biomechanics returned to normal following surgery. FINDINGS: Male peak knee adduction moment (p < 0.001) and impulse (p < 0.001) decreased six months following arthroplasty, whilst gait in women remained unchanged after surgery. Obesity did not influence gait changes in men or women. Gait of female arthroplasty participants did not differ from female controls after surgery except for sagittal plane knee range of motion (p = 0.003), whilst men differed from controls for peak knee adduction moment (p = 0.011), knee range of motion (p < 0.001), and peak knee flexion moment (p < 0.001). INTERPRETATION: Sex, but not obesity, influenced changes in gait biomechanics after arthroplasty. Men retained abnormal gait patterns after surgery, whilst women did not. Further research should determine the long-term implications of gait abnormalities seen in men after arthroplasty.

Trajectories of adherence to home-based exercise programs among people with knee osteoarthritis.

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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)). CONCLUSION: 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.

Moderators and mediators of effects of unloading shoes on knee pain in people with knee osteoarthritis: an exploratory analysis of the SHARK randomised controlled trial.

OBJECTIVE: To investigate moderators and biomechanical mediators of effects of unloading shoes on knee pain in people with knee osteoarthritis (OA). METHODS: Exploratory analysis from 164 participants in a clinical trial comparing unloading (ASICS GEL-Melbourne OA) to conventional walking shoes. The primary outcome was 6-month change in knee pain (11-point numerical rating scale (NRS)). Moderators included baseline peak knee adduction moment (KAM), radiographic severity (Kellgren & Lawrence (KL) scale), body mass, foot posture, neuropathic pain and diffuse knee pain. Mediators included change in peak KAM and KAM impulse. RESULTS: Radiographic severity was the only moderator to interact with footwear group (P = 0.02). Participants with KL = 2 experienced greater pain reductions with conventional compared to unloading shoes (mean difference in change in pain -1.64 units, 95% CI -3.07, -0.21), while unloading shoes tended to result in greater pain reductions than conventional shoes in KL = 3 (0.98, 95% CI -0.44, 2.39) and KL = 4 (0.64, 95% CI -0.64, 1.93). No variable showed any significant mediating effect in the entire cohort. However, there was some evidence that unloading shoes may reduce pain through reductions in peak KAM (indirect effect -0.31, 95% CIs -0.65, 0.03; P = 0.07) in people with KL ≥ 3, compared to conventional shoes. CONCLUSION: Unloading shoes conferred additional symptomatic benefits over conventional shoes in people with moderate to severe knee OA. There was some evidence effects may be mediated by a reduction in peak KAM. However, we were underpowered for subgroup analyses. These patients may represent a subgroup to which biomechanical interventions designed to reduce the KAM may be more effectively targeted.

The influence of sex and obesity on gait biomechanics in people with severe knee osteoarthritis scheduled for arthroplasty.

BACKGROUND: Sex and body mass may influence knee biomechanics associated with poor total knee arthroplasty (TKA) outcomes for knee osteoarthritis (OA). This study aimed to determine if gait differed between men and women, and overweight and class I obese patients with severe knee OA awaiting TKA. METHODS: 34 patients with severe knee OA (average age 70.0 (SD 7.2) years, body mass index 30.3 (4.1kg/m2)) were recruited from a TKA waiting list. Three-dimensional gait analysis was performed at self-selected walking speed. Comparisons were made between men and women, and overweight (body mass index (BMI) 25.0-29.9kg/m2) and class I obese (BMI 30.0-34.9kg/m2) participants. Biomechanical outcomes included absolute and body size-adjusted peak knee adduction moment (KAM), KAM impulse, peak knee flexion moment, as well as peak knee flexion and varus-valgus angles, peak varus-valgus thrust, and peak vertical ground reaction force (GRF). FINDINGS: Men had a higher absolute peak KAM, KAM impulse and peak GRF compared to women, and this sex-difference in frontal plane moments remained after adjusting for body size. However, when additionally adjusting for static knee alignment, differences disappeared. Knee biomechanics were similar between obesity groups after adjusting for the greater body weight of those with class I obesity. INTERPRETATION: Men had greater KAM and KAM impulse even after adjustment for body size; however adjustment for their more varus knees removed this difference. Obesity group did not influence knee joint kinematics or moments. This suggests sex- and obesity-differences in these variables may not be associated with TKA outcomes.

Longitudinal association between foot and ankle symptoms and worsening of symptomatic radiographic knee osteoarthritis: data from the osteoarthritis initiative.

OBJECTIVE: To assess whether foot and/or ankle symptoms are associated with an increased risk of worsening of knee pain and radiographic change in people with knee osteoarthritis (OA). METHODS: The presence and laterality of foot/ankle symptoms were recorded at baseline in 1368 participants from the Osteoarthritis Initiative (OAI) with symptomatic radiographic knee OA. Knee pain severity (measured using the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale) and minimum medial tibiofemoral joint space (minJSW) width measured on X-ray were assessed yearly over the subsequent 4 years. Associations between foot/ankle symptoms and worsening of (1) knee pain, and (2) both knee pain and minJSW (i.e., symptomatic radiographic knee OA) were assessed using logistic regression. RESULTS: Foot/ankle symptoms in either foot/ankle significantly increased the odds of knee pain worsening (adjusted OR 1.54, 95% CI 1.25 to 1.91). Laterality analysis showed ipsilateral (adjusted OR 1.50, 95% CI 1.07 to 2.10), contralateral (adjusted OR 1.44, 95% CI 1.02 to 2.06) and bilateral foot/ankle symptoms (adjusted OR 1.61, 95% CI 1.22 to 2.13) were all associated with knee pain worsening in the follow up period. There was no association between foot/ankle symptoms and worsening of symptomatic radiographic knee OA. CONCLUSION: The presence of foot/ankle symptoms in people with symptomatic radiographic knee OA was associated with increased risk of knee pain worsening, but not worsening of symptomatic radiographic knee OA, over the subsequent 4 years. Future studies should investigate whether treatment of foot/ankle symptoms reduces the risk of knee pain worsening in people with knee OA.

Assessing contemporary intensive care unit outcome: development and validation of the Australian and New Zealand Risk of Death admission model.

The Australian and New Zealand Risk of Death (ANZROD) model currently used for benchmarking intensive care units (ICUs) in Australia and New Zealand utilises physiological data collected up to 24 hours after ICU admission to estimate the risk of hospital mortality. This study aimed to develop the Australian and New Zealand Risk of Death admission (ANZROD0) model to predict hospital mortality using data available at presentation to ICU and compare its performance with the ANZROD in Australian and New Zealand hospitals. Data pertaining to all ICU admissions between 1 January 2006 and 31 December 2015 were extracted from the Australian and New Zealand Intensive Care Society Adult Patient Database. Hospital mortality was modelled using logistic regression with development (two-thirds) and validation (one-third) datasets. All predictor variables available at ICU admission were considered for inclusion in the ANZROD0 model. Model performance was assessed using Brier score, standardised mortality ratio and area under the receiver operating characteristic curve. The relationship between ANZROD0 and ANZROD predicted risk of death was assessed using linear regression. After standard exclusions, 1,097,416 patients were available for model development and validation. Observed mortality was 9.5%. Model performance measures (Brier score, standardised mortality ratio and area under the receiver operating characteristic curve) for the ANZROD0 and ANZROD in the validation dataset were 0.069, 1.0 and 0.853; 0.057, 1.0 and 0.909, respectively. There was a strong positive correlation between the mortality predictions with an overall R2 of 0.73. We found that the ANZROD0 model had acceptable calibration and discrimination. Predictions from the models had high correlations in all major diagnostic groups, with the exception of cardiac surgery and possibly trauma and sepsis.

Associations between changes in knee pain location and clinical symptoms in people with medial knee osteoarthritis using footwear for self-management: an exploratory study.

OBJECTIVE: To examine whether change in pain location is associated with clinically-relevant improvements in walking pain severity and physical dysfunction in people with medial tibiofemoral osteoarthritis (OA) using footwear for self-management. DESIGN: We analysed a sub-set of 91 participants pooled from both arms of a 6-month randomised controlled trial of footwear for knee OA. The Photographic Knee Pain Map was self-administered to generate changes in the number of painful zones ('unchanged', 'increased', 'decreased') and anatomical patterns of pain ('unchanged', 'no longer diffuse', 'becoming diffuse', 'other pattern changes'). Improvement in symptoms was determined using the minimum clinically important differences (MCIDs) in pain severity on a numeric rating scale, and function with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Fisher's exact tests examined differences in symptom improvement across categories of change and odds ratios (ORs, 95% CI) were calculated (adjusted for treatment allocation). RESULTS: Seventy-four percent (n = 67) of participants reported a change in pain location, and 46-50% (n = 42-45) reported clinically-relevant improvements in pain and function respectively. Fewer participants 'becoming diffuse' reported improved pain (n = 0, 0%) when compared to the other pattern change categories (P = 0.012). Participants with 'no longer diffuse' (OR (95% CI) = 0.3 (0.1-0.9) or 'becoming diffuse' (OR (95% CI) = 0.0 (0.0-0.4) pain patterns had significantly lower odds of improved function than those with 'other pattern changes'. CONCLUSION: Participants either developing into, or changing from, diffuse pain patterns were less likely to experience improvement in pain and/or function when self-managing with footwear.

Intraoperative dexamethasone does not increase the risk of postoperative wound infection: a propensity score-matched post hoc analysis of the ENIGMA-II trial (EnDEX).

BACKGROUND: In a post hoc analysis of the ENIGMA-II trial, we sought to determine whether intraoperative dexamethasone was associated with adverse safety outcomes. METHODS: Inverse probability weighting with estimated propensity scores was used to determine the association of dexamethasone administration with postoperative infection, quality of recovery, and adverse safety outcomes for 5499 of the 7112 non-cardiac surgery subjects enrolled in ENIGMA-II. RESULTS: Dexamethasone was administered to 2178 (40%) of the 5499 subjects included in this analysis and was not associated with wound infection [189 (8.7%) vs 275 (8.3%); propensity score-adjusted relative risk (RR) 1.10; 95% confidence interval (CI) 0.89-1.34; P=0.38], severe postoperative nausea and vomiting on day 1 [242 (7.3%) vs 189 (8.7%); propensity score-adjusted RR 1.06; 95% CI 0.86-1.30; P=0.59], quality of recovery score [median 14, interquartile range (IQR) 12-15, vs median 14, IQR 12-16, P=0.10), length of stay in the postanaesthesia care unit [propensity score-adjusted median (IQR) 2.0 (1.3, 2.9) vs 1.9 (1.3, 3.1), P=0.60], or the primary outcome of the main trial. Dexamethasone administration was associated with a decrease in fever on days 1-3 [182 (8.4%) vs 488 (14.7%); RR 0.61; 95% CI 0.5-0.74; P<0.001] and shorter lengths of stay in hospital [propensity score-adjusted median (IQR) 5.0 (2.9, 8.2) vs 5.3 (3.1, 9.1), P<0.001]. Neither diabetes mellitus nor surgical wound contamination status altered these outcomes. CONCLUSION: Dexamethasone administration to high-risk non-cardiac surgical patients did not increase the risk of postoperative wound infection or other adverse events up to day 30, and appears to be safe in patients either with or without diabetes mellitus. CLINICAL TRIAL REGISTRATION: NCT00430989.

Safety of sedation for gastrointestinal endoscopy in a group of university-affiliated hospitals: a prospective cohort study.

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.

The relationship between foot and ankle symptoms and risk of developing knee osteoarthritis: data from the osteoarthritis initiative.

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.