Aliya Sarmanova

Synovial changes detected by ultrasound in people with knee osteoarthritis - a meta-analysis of observational studies.

Summary Objectives To examine the prevalence of synovial effusion, synovial hypertrophy and positive Doppler signal (DS) detected by ultrasound (US) in people with knee osteoarthritis (OA) and/or knee pain compared to that in the general population. Method A systematic literature search was undertaken in Medline, EMBASE, Allied and Complementary Medicine, PubMed Web of Science, and SCOPUS databases in May 2015. Frequencies of US abnormalities in people with knee OA/pain, in the general population or asymptomatic controls were pooled using the random effects model. Publication bias and heterogeneity between studies were examined. Results Twenty four studies in people with knee pain/OA and five studies of the general population or asymptomatic controls met the inclusion criteria. The pooled prevalence of US effusion, synovial hypertrophy and positive DS in people with knee OA/pain were 51.5% (95% CI 40.2 to 62.8), 41.5% (26.3–57.5) and 32.7% (8.34–63.24), respectively, which were higher than those in the general population or asymptomatic controls (19.9% (95%CI 7.8–35.3%), 14.5% (0–58.81), and 15.8 (3.08–35.36), respectively). People with knee OA (ACR criteria or radiographic OA) had greater prevalence of US abnormalities than people with knee pain (P = 0.037, P = 0.010 and P = 0.009, respectively). Conclusions US detected effusion, synovial hypertrophy and DS are more common in people with knee OA/pain, compared to the general population. These abnormalities relate more to presence of OA structural changes than to pain.

Relative efficacy and safety of topical non-steroidal anti-inflammatory drugs for osteoarthritis: a systematic review and network meta-analysis of randomised controlled trials and observational studies

Objectives To compare the efficacy and safety of topical non-steroidal anti-inflammatory drugs (NSAIDs), including salicylate, for the treatment of osteoarthritis (OA). Methods PubMed, Embase, Cochrane Library and Web of Science were searched from 1966 to January 2017. Randomised controlled trials (RCTs) comparing topical NSAIDs with placebo or each other in patients with OA and observational studies comparing topical NSAIDs with no treatment or each other irrespective of disease were included. Two investigators identified studies and independently extracted data. Bayesian network and conventional meta-analyses were conducted. The primary outcomes were pain relief for RCTs and risk of adverse effects (AEs) for observational studies. Results 43 studies, comprising 36 RCTs (7 900 patients with OA) and seven observational studies (218 074 participants), were included. Overall, topical NSAIDs were superior to placebo for relieving pain (standardised mean difference (SMD)=−0.30, 95% CI −0.40 to –0.20) and improving function (SMD=−0.35, 95% CI −0.45 to –0.24) in OA. Of all topical NSAIDs, diclofenac patches were most effective for OA pain (SMD=−0.81, 95% CI −1.12 to –0.52) and piroxicam was most effective for functional improvement (SMD=−1.04, 95% CI −1.60 to –0.48) compared with placebo. Although salicylate gel was associated with higher withdrawal rates due to AEs, the remaining topical NSAIDs were not associated with any increased local or systemic AEs. Conclusions Topical NSAIDs were effective and safe for OA. Diclofenac patches may be the most effective topical NSAID for pain relief. No serious gastrointestinal and renal AEs were observed in trials or the general population. However, confirmation of the cardiovascular safety of topical NSAIDs still warrants further observational study.

The placebo effect and its determinants in fibromyalgia: meta-analysis of randomised controlled trials

The aims of this study were to determine whether placebo treatment in randomised controlled trials (RCTs) is effective for fibromyalgia and to identify possible determinants of the magnitude of any such placebo effect. A systematic literature search was undertaken for RCTs in people with fibromyalgia that included a placebo and/or a no-treatment (observation only or waiting list) control group. Placebo effect size (ES) for pain and other outcomes was measured as the improvement of each outcome from baseline divided by the standard deviation of the change from baseline. This effect was compared with changes in the no-treatment control groups. Meta-analysis was undertaken to combine data from different studies. Subgroup analysis was conducted to identify possible determinants of the placebo ES. A total of 3912 studies were identified from the literature search. After scrutiny, 229 trials met the inclusion criteria. Participants who received placebo in the RCTs experienced significantly better improvements in pain, fatigue, sleep quality, physical function, and other main outcomes than those receiving no treatment. The ES of placebo for pain relief was clinically moderate (0.53, 95%CI 0.48 to 0.57). The ES increased with increasing strength of the active treatment, increasing participant age and higher baseline pain severity, but decreased in RCTS with more women and with longer duration of fibromyalgia. In addition, placebo treatment in RCTs is effective in fibromyalgia. A number of factors (expected strength of treatment, age, gender, disease duration) appear to influence the magnitude of the placebo effect in this condition.

Conventional and biologic disease-modifying anti-rheumatic drugs for osteoarthritis: a meta-analysis of randomized controlled trials

Abstract Objectives The role of inflammation in OA is controversial and it is unclear whether suppressing inflammation with conventional or biologic DMARDs is effective. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to compare DMARDs with placebo in participants with symptomatic OA. Methods Databases (Medline, Embase, Allied and Complementary Medicine Database, Web of Science and Cochrane Library), conference abstracts and ClinicalTrials.gov were searched to end of November 2017 for placebo-controlled RCTs of DMARDs, including biologics, in symptomatic OA. Pain data at treatment peak time point were extracted and combined using a random-effects meta-analysis. Markers of inflammation and adverse events were extracted and reviewed. Risk of bias assessment was conducted using Cochrane’s tool. Results Eleven RCTs (1205 participants) were meta-analysed, including six for conventional DMARDs (757 participants) and five for biologics (448 participants). Overall, DMARDs were statistically superior to placebo [effect size (ES) = 0.18, 95% CI: 0.03, 0.34], although the difference was not clinically significant (0.5 ES threshold). Furthermore, no statistically significant differences were observed in sub-analysis of high-quality trials (ES = 0.11, 95% CI : −0.06, 0.28), biologics (ES = 0.16, 95% CI: −0.02, 0.34) or conventional DMARDs (ES = 0.24, 95% CI: −0.05, 0.54). No difference was found between erosive vs non-erosive hand OA, hand vs knee OA or anti-IL1 vs anti-TNF biologics. Conclusion DMARDs did not offer clinically significant pain relief above placebo in OA. This poor efficacy indicates that inflammation may not be a prime driver for OA pain.

Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial

Summary Background In the UK, gout management is suboptimum, with only 40% of patients receiving urate-lowering therapy, usually without titration to achieve a target serum urate concentration. Nurses successfully manage many diseases in primary care. We compared nurse-led gout care to usual care led by general practitioners (GPs) for people in the community. Methods Research nurses were trained in best practice management of gout, including providing individualised information and engaging patients in shared decision making. Adults who had experienced a gout flare in the previous 12 months were randomly assigned 1:1 to receive nurse-led care or continue with GP-led usual care. We assessed patients at baseline and after 1 and 2 years. The primary outcome was the percentage of participants who achieved serum urate concentrations less than 360 μmol/L (6 mg/dL) at 2 years. Secondary outcomes were flare frequency in year 2, presence of tophi, quality of life, and cost per quality-adjusted life-year (QALY) gained. Risk ratios (RRs) and 95% CIs were calculated based on intention to treat with multiple imputation. This study is registered with www.ClinicalTrials.gov, number NCT01477346. Findings 517 patients were enrolled, of whom 255 were assigned nurse-led care and 262 usual care. Nurse-led care was associated with high uptake of and adherence to urate-lowering therapy. More patients receiving nurse-led care had serum urate concentrations less than 360 μmol/L at 2 years than those receiving usual care (95% vs 30%, RR 3·18, 95% CI 2·42–4·18, p<0·0001). At 2 years all secondary outcomes favoured the nurse-led group. The cost per QALY gained for the nurse-led intervention was £5066 at 2 years. Interpretation Nurse-led gout care is efficacious and cost-effective compared with usual care. Our findings illustrate the benefits of educating and engaging patients in gout management and reaffirm the importance of a treat-to-target urate-lowering treatment strategy to improve patient-centred outcomes. Funding Arthritis Research UK.

Comment on: Conventional and biologic disease-modifying anti-rheumatic drugs for osteoarthritis: a meta-analysis of randomized controlled trials: reply

MD reports a grant from AstraZeneca funding a non-drug PI-led study in Nottingham (Sons of Gout study) and honoraria for Advisory boards on osteoarthritis and gout for AstraZeneca, Grunenthal, Mallinckrodt, and Roche, outside the submitted work. WZ reports honoraria for Grunenthal and speaker fees for Bioiberica and Hisun, outside the submitted work. All other authors have declared no conflicts of interest.

Contribution of central and peripheral risk factors to prevalence, incidence and progression of knee pain: a community-based cohort study

Summary Aim To explore risk factors that may influence knee pain (KP) through central or peripheral mechanisms. Methods A questionnaire-based prospective community cohort study with KP defined as pain in or around a knee on most days for at least a month. Baseline prevalence, and one year incidence and progression (KP worsening) were examined. Central (e.g., Pain Catastrophizing Scale (PCS)) and peripheral (e.g., significant injury) risk factors were examined. Adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated using logistic regression. Proportional risk contribution (PRC) was estimated using receiver-operator-characteristic (ROC) analysis. Results Of 9506 baseline participants, 4288 (45%) had KP (men 1826; women, 2462). KP incidence was 12% (men 11%, women 13%), and KP progression 19% (men 16%, women 21%) at one year. While both central and peripheral factors contributed to prevalence, central factors contributed more to progression, and peripheral factors more to incidence of KP. For example, although PCS (OR 2.06, 95% CI 1.88–2.25) and injury (5.62, 4.92–6.42) associated with KP prevalence, PCS associated with progression (2.27, 1.83–2.83) but not incidence (1.14, 0.86–1.52), whereas injury more strongly associated with incidence (69.27, 24.15–198.7) than progression (2.52, 1.48–4.30). The PRC of central and peripheral factors were 19% and 23% for prevalence, 14% and 29% for incidence, and 29% and 5% for progression, respectively. Conclusions Both central and peripheral risk factors influence KP but relative contributions may differ in terms of development (mainly peripheral) and progression (mainly central). Further study of such relative contributions may inform primary and secondary prevention strategies.

Proportion of contextual effects in the treatment of fibromyalgia—a meta-analysis of randomised controlled trials

The objective of this study is to examine the proportion of the total treatment effect that is attributable to contextual effects in randomised controlled trials (RCTs) of treatments for fibromyalgia. A systematic literature search was undertaken in Medline, Web of Science, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Allied and Complementary Medicine in September 2015. The proportion of contextual effect (PCE) was calculated by dividing the improvement in the placebo arm by the improvement in the treatment arm. The measure was log-transformed for each trial and the random effects model was used to pool data. The primary outcome was pain. Secondary outcomes were fibromyalgia impact questionnaire (FIQ) total and fatigue. Heterogeneity was quantified using I2. Publication bias was assessed using a funnel plot and Egger’s test. Subgroup analysis was undertaken to explore heterogeneity and potential determinants of the PCE. Fifty-one eligible trials (9599 participants) were identified. The PCE was 0.60 (95% CI 0·56 to 0·64) for pain, 0·57 (95% CI 0·53 to 0·61) for FIQ total, and 0·63 (95% CI 0·59 to 0·68) for fatigue. The I2 was 99.4% for pain, 99.2% for FIQ total, and 97.6% for fatigue. More than half of the treatment effect in fibromyalgia RCTs results from non-specific contextual factors. This suggests that optimising contextual care may enhance treatment effects and improve outcomes. Reporting the total treatment effect and the proportion of contextual effect in trials may help to better translate research evidence into practice.