Efficacy, safety, and dose-dependence of the analgesic effects of opioid therapy for people with osteoarthritis: systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of opioids for analgesic therapy for people with osteoarthritis. STUDY DESIGN: Systematic review and meta-analysis of randomised, placebo-controlled trials of opioid therapies for treating the pain of osteoarthritis. The primary outcome was medium term pain relief (six weeks to less than 12 months). Quality of evidence was assessed with GRADE criteria. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and Central Register of Controlled Trials, CINAHL, PsycINFO, AMED, and the WHO International Clinical Trials Registry; trials published to 31 October 2020. DATA SYNTHESIS: We extracted pain, disability, health-related quality of life, and adverse events data for 36 eligible trials (overall dose range: 10-210 oral morphine milligram equivalents [MME] per day). Continuous pain and disability outcomes were converted to common 0-100-point scales; changes of less than ten points were deemed to be very small effects. Differences in dichotomous outcomes were expressed as risk ratios. Data were pooled for meta-analysis in random effects models. The evidence from 19 trials (8965 participants; dose range, 10-126 MME/day) for very small medium term pain relief (mean difference [MD], -4.59 points; 95% CI, -7.17 to -2.02 points) was low quality, as was that from 16 trials (6882 participants; dose range, 10-126 MME/day) for a very small effect on disability (MD, -4.15 points; 95% CI, -6.94 to -1.35 points). Opioid dose was not statistically significantly associated with either degree of pain relief or incidence of adverse events in a meta-regression analysis. Evidence that opioid therapy increased the risk of adverse events (risk ratio, 1.43; 95% CI, 1.29-1.59) was of very low quality. CONCLUSIONS: Opioid medications may provide very small pain and disability benefits for people with osteoarthritis, but may also increase the risk of adverse events. PROSPERO REGISTRATION: CRD42019142813 (prospective).

OPAL: a randomised, placebo-controlled trial of opioid analgesia for the reduction of pain severity in people with acute spinal pain-a statistical analysis plan.

BACKGROUND: Low back and neck pain are a leading cause of disease burden globally. Opioids are recommended in guidelines for acute low back and neck pain; however, there is a lack of compelling efficacy data to support this. METHODS: The OPAL trial is a prospectively registered, triple-blinded, randomised, placebo-controlled trial. Patients with acute (≤12 weeks duration) back and/or neck pain receive guideline care plus either an opioid (oxycodone + naloxone, up to 20 mg per day) or a placebo for up to 6 weeks or earlier, if pain is resolved. The primary outcome is pain measured using the Pain Severity Score of the Brief Pain Inventory with the primary time point being 6 weeks. Secondary outcomes include physical function, time to recovery, quality of life, adverse events and risk of opioid misuse. Outcomes are collected at weeks 2, 4, 6, 12, 26 and 52. Analysis will be done on an intention-to-treat principle. p values of < 0.05 will be considered significant and 95% confidence intervals will be reported. Repeated-measures linear mixed models will be used to assess the effect of the treatment group on the primary outcome and continuous secondary outcomes. Adverse events will be compared between groups using Fisher's exact test. Cost-effectiveness analyses will be conducted if a treatment effect on pain is seen at week 6. Subgroup analyses will be performed to assess whether pain duration and pain location are treatment effect modifiers. DISCUSSION: The OPAL trial will provide important evidence about whether a short course of opioids is effective in the treatment of acute non-specific low back and/or neck pain. This pre-specified statistical analysis plan details the methodology for the analysis of the OPAL trial results. TRIAL REGISTRATION: ACTRN12615000775516 . The trial has completed recruitment. Follow-up on the last patient will be completed in March 2022.

The impact of a patient decision aid on intention to undergo surgery for subacromial pain syndrome: An online randomised controlled trial.

OBJECTIVE: To evaluate the effects of a patient decision aid for people considering shoulder surgery. METHODS: Participants with shoulder pain considering shoulder surgery (n = 425) were recruited online and randomised to (i) a decision aid outlining the benefits and harms of shoulder surgery and non-surgical options (then randomised to a side-by-side vs. top-and-bottom display of options); and (ii) general information about shoulder pain from the NHS. Outcomes included treatment intention (primary), knowledge, attitudes, informed choice, and decisional conflict. Linear and logistic regression models were used to evaluate between-groups differences in outcomes. RESULTS: 409 participants (96%) had post-intervention data. Mean age was 41.3 years, 44.2% were female. There was no between-group difference in post-intervention treatment intention (MD -0.2, 95% CI: -3.3 to 2.8) and likelihood of intending to have shoulder surgery (OR 0.7, 95% CI: 0.3-1.5). The decision aid slightly improved knowledge (MD 4.4, 95% CI: 0.2-8.6), but not any other secondary outcomes. The display of options did not influence any outcome. CONCLUSIONS: In this online trial, a co-designed patient decision aid had no effect on treatment intention, attitudes, informed choice, and decisional conflict, but a small effect on improving knowledge. PRACTICE IMPLICATIONS: Research is needed to understand reasons for the lack of anticipated effects. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry (ACTRN12621000992808).

Advice and education provide small short-term improvements in pain and disability in people with non-specific spinal pain: a systematic review.

QUESTIONS: What is the effect of advice/education compared with placebo or no advice/education on pain and disability in people with non-specific spinal pain? To what extent do characteristics of the patients, trial or intervention modify the estimate of the treatment effects? DESIGN: A systematic review with meta-analyses of randomised controlled trials. PARTICIPANTS: Adults with non-specific back and/or neck pain with or without radiating leg/arm pain of any duration were included. Trials recruiting pregnant women or surgical patients in the immediate postoperative phase were ineligible. INTERVENTION: Advice or education. OUTCOME MEASURES: The primary outcomes were self-reported pain and disability, and the secondary outcome was adverse events. The following potential effect modifiers were examined: risk of bias, duration of pain, location of pain, intensity of intervention and mode of intervention. RESULTS: Twenty-seven trials involving 7,006 participants were included. Eighteen of the included trials were assessed as being at low risk of bias (≥ 6 on the PEDro scale). There was low-quality evidence that advice had a small effect on pain (MD -8.2, 95% CI -12.5 to -3.9, n = 2,241) and moderate-quality evidence that advice had a small effect on disability (MD -4.5, 95% CI -7.9 to -1.0, n = 2,579) compared with no advice or placebo advice in the short-term. None of the items that were assessed modified the treatment effects. CONCLUSION: Advice provides short-term improvements in pain and disability in non-specific spinal pain, but the effects are small and may be insufficient as the sole treatment for patients with spinal pain. REGISTRATION: PROSPERO CRD42020162008.