IMPORTANCE: Osteoarthritis (OA) of the knee is the most frequent form of arthritis and a cause of pain and disability. Combined nonpharmacologic and pharmacologic treatments are recommended as the optimal treatment approach, but no evidence supports the recommendation.

OBJECTIVE: To assess the clinical benefits of an intra-articular corticosteroid injection given before exercise therapy in patients with OA of the knee.

DESIGN, SETTING, AND PARTICIPANTS: We performed a randomized, blinded, placebo-controlled clinical trial evaluating the benefit of intra-articular corticosteroid injection vs placebo injection given before exercise therapy at an OA outpatient clinic from October 1, 2012, through April 2, 2014. The participants had radiographic confirmation of clinical OA of the knee, clinical signs of localized inflammation in the knee, and knee pain during walking (score >4 on a scale of 0 to 10).

INTERVENTIONS: Participants were randomly allocated (1:1) to an intra-articular 1-mL injection of the knee with methylprednisolone acetate (Depo-Medrol), 40 mg/mL, dissolved in 4 mL of lidocaine hydrochloride (10 mg/mL) (corticosteroid group) or a 1-mL isotonic saline injection mixed with 4 mL of lidocaine hydrochloride (10 mg/mL) (placebo group). Two weeks after the injections, all participants started a 12-week supervised exercise program.

MAIN OUTCOMES AND MEASURES: The primary outcome was change in the Pain subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire (range, 0-100; higher scores indicate greater improvement) at week 14. Secondary outcomes included the remaining KOOS subscales and objective measures of physical function and inflammation. Outcomes were measured at baseline, week 2 (exercise start), week 14 (exercise stop), and week 26 (follow-up).

RESULTS: One hundred patients were randomized to the corticosteroid group (n = 50) or the placebo group (n = 50); 45 and 44 patients, respectively, completed the trial. The mean (SE) changes in the KOOS Pain subscale score at week 14 were 13.6 (1.8) and 14.8 (1.8) points in the corticosteroid and placebo groups, respectively, corresponding to a statistically insignificant mean difference of 1.2 points (95% CI, -3.8 to 6.2; P = .64). We found no statistically significant group differences in any of the secondary outcomes at any time point.

CONCLUSIONS AND RELEVANCE: No additional benefit results from adding an intra-articular injection of 40 mg of corticosteroid before exercise in patients with painful OA of the knee. Further research is needed to establish optimal and potentially synergistic combinations of conservative treatments.

TRIAL REGISTRATION: clinicaltrialsregister.eu Identifier: 2012-002607-18; clinicaltrials.gov Identifier: NCT01945749.

OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis (RA) Flare Group was established to develop an approach to identify and measure RA flares. An overview of our OMERACT 2014 plenary is provided.

METHODS: Feasibility and validity of flare domains endorsed at OMERACT 11 (2012) were described based on initial data from 3 international studies collected using a common set of questions specific to RA flare. Mean flare frequency, severity, and duration data were presented, and domain scores were compared by flare status to examine known-groups validity. Breakout groups provided input for stiffness, self-management, contextual factors, and measurement considerations.

RESULTS: Flare data from 501 patients in an observational study indicated 39% were in flare, with mean (SD) severity of 6.0 (2.6) and 55% lasting > 14 days. Pain, physical function, fatigue, participation, and stiffness scores averaged ≥ 2 times higher (2 of 11 points) in flaring individuals. Correlations between flare domains and corresponding legacy instruments were obtained: r = 0.46 to 0.93. A combined definition (patient report of flare and 28-joint Disease Activity Score increase) was evaluated in 2 other trials, with similar results. Breakout groups debated specific measurement issues.

CONCLUSION: These data contribute initial evidence of feasibility and content validation of the OMERACT RA Flare Core Domain Set. Our research agenda for OMERACT 2016 includes establishing duration/intensity criteria and developing criteria to identify RA flares using existing disease activity measures. Ongoing work will also address discordance between patient and physician ratings, facilitate application of flare criteria to clinical care, elucidate the role of self-management, and finalize recommendations for RA flare measurement.

Knee osteoarthritis (OA) is a common disease that impairs walking ability and function. We compared the temporal gait variability and motor control in people with knee OA with healthy controls. The purpose was to test the hypothesis that the temporal gait variability would reflect a more stereotypic pattern in people with knee OA compared with healthy age-matched subjects. To assess the gait variability the temporal structure of the ankle and knee joint kinematics was quantified by the largest Lyapunov exponent and the stride time fluctuations were quantified by sample entropy and detrended fluctuation analysis. The motor control was assessed by the soleus (SO) Hoffmann (H)-reflex modulation and muscle co-activation during walking. The results showed no statistically significant mean group differences in any of the gait variability measures or muscle co-activation levels. The SO H-reflex amplitude was significantly higher in the knee OA group around heel strike when compared with the controls. The mean group difference in the H-reflex in the initial part of the stance phase (control-knee OA) was -6.6% Mmax (95% CI: -10.4 to -2.7, p=0.041). The present OA group reported relatively small impact of their disease. These results suggest that the OA group in general sustained a normal gait pattern with natural variability but with suggestions of facilitated SO H-reflex in the swing to stance phase transition. We speculate that the difference in SO H-reflex modulation reflects that the OA group increased the excitability of the soleus stretch reflex as a preparatory mechanism to avoid sudden collapse of the knee joint which is not uncommon in knee OA.

Childhood acute lymphoblastic leukemia survival approaches 90%. New strategies are needed to identify the 10-15% who evade cure. We applied targeted, sequencing-based genotyping of 25 000 to 34 000 preselected potentially clinically relevant single-nucleotide polymorphisms (SNPs) to identify host genome profiles associated with relapse risk in 352 patients from the Nordic ALL92/2000 protocols and 426 patients from the German Berlin-Frankfurt-Munster (BFM) ALL2000 protocol. Patients were enrolled between 1992 and 2008 (median follow-up: 7.6 years). Eleven cross-validated SNPs were significantly associated with risk of relapse across protocols. SNP and biologic pathway level analyses associated relapse risk with leukemia aggressiveness, glucocorticosteroid pharmacology/response and drug transport/metabolism pathways. Classification and regression tree analysis identified three distinct risk groups defined by end of induction residual leukemia, white blood cell count and variants in myeloperoxidase (MPO), estrogen receptor 1 (ESR1), lamin B1 (LMNB1) and matrix metalloproteinase-7 (MMP7) genes, ATP-binding cassette transporters and glucocorticosteroid transcription regulation pathways. Relapse rates ranged from 4% (95% confidence interval (CI): 1.6-6.3%) for the best group (72% of patients) to 76% (95% CI: 41-90%) for the worst group (5% of patients, P<0.001). Validation of these findings and similar approaches to identify SNPs associated with toxicities may allow future individualized relapse and toxicity risk-based treatments adaptation.Leukemia advance online publication, 25 July 2014; doi:10.1038/leu.2014.205.

INTRODUCTION: Current pharmacological therapies in patients with type 2 diabetes (T2D) are challenged by lack of sustainability and borderline firm evidence of real long-term health benefits. Accordingly, lifestyle intervention remains the corner stone in the management of T2D. However, there is a lack of knowledge regarding the optimal intervention programmes in T2D ensuring both compliance as well as long-term health outcomes. Our objective is to assess the effects of an intensive lifestyle intervention (the U-TURN intervention) on glycaemic control in patients with T2D. Our hypothesis is that intensive lifestyle changes are equally effective as standard diabetes care, including pharmacological treatment in maintaining glycaemic control (ie, glycated haemoglobin (HbA1c)) in patients with T2D. Furthermore, we expect that intensive lifestyle changes will decrease the need for antidiabetic medications.

METHODS AND ANALYSIS: The study is an assessor-blinded, parallel group and a 1-year randomised trial. The primary outcome is change in glycaemic control (HbA1c), with the key secondary outcome being reductions in antidiabetic medication. Participants will be patients with T2D (T2D duration <10 years) without complications who are randomised into an intensive lifestyle intervention (U-TURN) or a standard care intervention in a 2:1 fashion. Both groups will be exposed to the same standardised, blinded, target-driven pharmacological treatment and can thus maintain, increase, reduce or discontinue the pharmacological treatment. The decision is based on the standardised algorithm. The U-TURN intervention consists of increased training and basal physical activity level, and an antidiabetic diet including an intended weight loss. The standard care group as well as the U-TURN group is offered individual diabetes management counselling on top of the pharmacological treatment.

ETHICS AND DISSEMINATION: This study has been approved by the Scientific Ethical Committee at the Capital Region of Denmark (H-1-2014-114). Positive, negative or inconclusive findings will be disseminated in peer-reviewed journals, at national and international conferences.

TRIAL REGISTRATION NUMBER: NCT02417012.

PURPOSE: To evaluate the efficacy of a specialized rosehip powder nutraceutical on the biomechanical function of the knee joint during walking in individuals with knee-related walking limitations.

METHODS: Randomized, participant and outcome assessor blinded trial. Participants with self-reported knee-related walking limitations were randomized (1:1) to receive three capsules/day of either rosehip powder or identically appearing placebo capsules for 12 weeks. At baseline and the 12 weeks follow-up, 3-dimensional gait analyses were performed from which the peak resultant knee moment was selected as primary outcome. Secondary outcomes included sagittal and frontal plane knee joint moments, knee joint kinematics, peaks in the vertical ground reaction forces, and self-selected walking speeds. Analyses were based on ANCOVA with the 'Intention-To-Treat' (ITT) population, defined as all randomized participants using last observation carried forward imputation for missing data.

RESULTS: 100 participants were randomized to rosehip (n=50) or placebo (n=50) and defined the ITT population. Of these 94 completed the study (47 in each group). There were statistically significant group differences in the change from baseline in the primary outcome: the resultant knee moment (0.06 nm/kg, 95%CI: 0.00-0.12; P=0.039) and in the peaks in the sagittal plane moments and kinematics during the stance phase of walking with the rosehip group exhibiting greater joint moments and more knee joint flexion during walking than the placebo group.

CONCLUSION: A daily intake of rosehip powder for 12 weeks improved important indices of knee joint function and dynamics during walking compared to placebo in persons with knee-related walking limitations.

OBJECTIVE: Despite solid evidence of an association between centralized body fatness and subsequent disease risk, little is known about the consequences of changes in body fat distribution. Recently it was shown that large hip circumference (HC), measured once, was protective against total and cardiovascular disease (CVD) mortality in women but that gain or loss in HC was unrelated to these outcomes. This study examines whether a 6-year change in waist circumference (WC) predicts mortality and CVD in the same study sample.

METHODS: Baseline WC and 6-year change in WC as predictors of mortality and CVD were analyzed in 2,492 women from the Danish MONICA study and the Prospective Population Study of Women in Gothenburg, Sweden.

RESULTS: Increase in WC was significantly associated with increased subsequent mortality and CVD adjusting for BMI and other covariates, with some evidence of a J-shaped association. Associations between increase in WC and outcomes were restricted to women with normal weight at baseline and to ever-smokers.

CONCLUSIONS: In contrast to changes in HC which did not predict mortality and CVD, a 6-year increase in WC is strongly predictive, particularly among initially lean women and ever-smokers. This implies the importance of developing strategies to prevent central fat deposition.