Chung-Wei Christine Lin

2 DREAM is a randomised, superiority, parallel-group, placebo-controlled, participant, clinician, and assessor blinded trial with an adaptive group sequential design that allows early stopping for efficacy or futility. The purpose is to investigate whether taking 60 mg of duloxetine daily for 12 weeks in addition to guideline-recommended advice, compared with placebo in addition to guideline-recommended advice, can reduce leg pain intensity in individuals with chronic sciatica. The primary outcome is leg pain intensity measured on a 0-10 numerical pain rating scale. It will be analysed using a repeated-measures linear mixed model. This statistical analysis plan pre-specifies the methods of analysis to be used in the interim analysis and the final analysis for the outcomes and key variables collected in the trial. It includes planned sensitivity analyses for the final analysis, including covariate adjustments and subgroup analyses, as well as the health economics analysis plan.

Objectives: This study aims to estimate the rate of recruitment of participants. Design: This is a pilot, multicentre, double-blind, placebo-controlled, randomised controlled trial of oral oxycodone and sublingual placebo vs sublingual buprenorphine and oral placebo for postoperative pain management for 7 days after pelvic exenteration. Setting: Patients will be recruited from three metropolitan quaternary referral centres that offer advanced gastrointestinal surgery in Australia. Participants: The inclusion criteria will be patients over the age of 18 years undergoing pelvic exenteration surgery and exclusion criteria are previous adverse events related to the study drugs, currently requiring monoamine oxidase inhibitor medications and if epidural analgesia is planned in the perioperative period. Interventions: Enrolled patients will undergo pelvic exenteration surgery and be initiated postoperatively on patient-controlled analgesia. In the postoperative period, when clinically appropriate to take oral medications, patients will be commenced on trial analgesia for 7 days. Participants will be randomised to receive either oral active oxycodone 5–10 mg up to 3 hourly as required (with sublingual placebo) or sublingual active buprenorphine 200–400 mcg 3 hourly as required (with oral placebo). Main outcome measures: The primary outcome measure is the rate of recruitment over a 6-month period. Secondary outcomes include an assessment of missing data, protocol adherence and acceptability of the trial to participants. Ethics and dissemination: The trial received ethics approval from Sydney Local Health District, Royal Prince Alfred Hospital Human Research Ethics Committee (No: X25-0128 & 2025/ETH01058). The results of the study will be disseminated by publication and presentation at local annual scientific meetings in Australia. Trial registration number: The study protocol is prospectively registered at the Australian New Zealand Clinical Trials Registry (ANZCTR) ( www.anzctr.org.au ; ACTRN12625000901404).

Introduction: Despite limited evidence of efficacy, opioid analgesics are frequently used by patients for chronic pain while awaiting total hip or knee arthroplasty (THA or TKA). Preoperative use of opioids is problematic as it increases the likelihood of postoperative opioid-related adverse drug events and postoperative complications and is the strongest predictor of persistent opioid use post surgery. Opioid tapering prior to elective surgery has been proposed as a strategy for mitigating harms and improving postoperative outcomes. This protocol describes a randomised clinical trial, which aims to determine the effectiveness of a preoperative pharmacist-partnered opioid tapering programme compared with standard care for patients awaiting elective THA or TKA on postoperative outcomes including persistent opioid use. Method and analysis: Eligible participants must be aged ≥18 years; awaiting elective unilateral or bilateral THA or TKA; speak and read English; use prescription opioid analgesics at least 4 days a week and have access to internet or telephone. The participants will be excluded if they are undergoing a repeat surgery (same procedure within 6 months), are using opioids for cancer, palliative care or substance use disorder; have previously or are currently undergoing an opioid tapering programme or active medication review or have cognitive impairment. Enrolled participants will be randomised in a 1:1 ratio in permuted blocks of two and four to: (1) intervention or (2) standard care. A total of 314 participants will be recruited into the study. The intervention will include a pharmacist-partnered opioid tapering programme in which a pharmacist will work with participants to reduce their opioid dose over a 3-month period before surgery. Standard care will involve review by the hospital preadmission clinic multidisciplinary team to assess medical, physical and psychological health prior to surgery and education sessions for preoperative and postoperative care. The primary outcome assessed is persistent opioid use 3 months post surgery. The key secondary outcome is total Western Ontario and McMaster Universities Arthritis Index score. Data analysis will be performed using an estimand framework, with a generalised estimating equation model for the primary outcome from 1 day to 3 days presurgery to 3 months post surgery and a multilevel model for the main secondary outcome from baseline to 3 months after surgery. Cost-effectiveness and cost-utility analyses will be conducted to determine whether the intervention is cost-effective from the healthcare system perspective. Ethics and dissemination: Ethics approval for this study was granted by a Human Research Ethics Committee (approval number: 2023/ETH01042). Results will be disseminated in peer reviewed journals, at international scientific meetings as well as meetings with key stakeholders and via the media. Trial registration number: ACTRN12623000685617.

Low back pain is the leading cause of disability worldwide. Research has associated Modic changes (signal changes in the vertebral endplate on magnetic resonance imaging (MRI)) with low back pain. Some hypothesise that Modic type 1 changes (oedema) may have an infective cause, and that antibiotics could serve as targeted treatment. To assess the benefits and harms of antibiotic therapy, compared with placebo or another treatment, in people with low back pain, radicular pain, or both. We searched CENTRAL, MEDLINE, Embase, and two trials registries up to 26 August 2025, with no restrictions related to language or date of publication. We included randomised controlled trials (RCTs) that assessed antibiotics versus placebo (primary comparison) or other treatments. We assessed the evidence separately for four populations of adults with low back pain, radicular pain, or both: those with 1) Modic type 1 changes and evidence of disc herniation, 2) other Modic changes and evidence of disc herniation, 3) any Modic changes but no evidence of disc herniation, and 4) evidence of disc herniation without any Modic changes. Critical outcomes were pain intensity and disability or function up to 12 to 14 weeks, and the number of participants with any adverse events and serious adverse events at the end of the trial period. Two review authors independently evaluated the risk of bias using the Cochrane risk of bias tool RoB 1. Two review authors independently screened studies and extracted data. We synthesised results for each outcome using random-effects meta-analysis. Where this was not possible due to the nature of the data, we reported the results descriptively. We used GRADE to assess the certainty of evidence. The primary comparison was antibiotics versus placebo in people with low back pain, radicular pain, or both, and Modic type 1 changes with evidence of disc herniation (population 1) up to 12 to 14 weeks. We included three trials, conducted in Denmark, Belgium, and Norway, with a total of 402 participants (mean ages ranged from 44.7 years to 51.0 years). Two trials recruited people with chronic (> 6 months) moderate-to-severe low back pain (with or without radicular pain), Modic changes, and disc herniation. One trial included people with Modic type 1 changes only (population 1) and compared oral amoxicillin-clavulanate 500 mg/125 mg to placebo (for both treatments, 1 or 2 tablets 3 times daily for 100 days). The second trial included people with either Modic type 1 changes (population 1) or Modic type 2 changes (population 2) and compared oral amoxicillin 750 mg to placebo (for both treatments, 3 times daily for 100 days). Follow-up was 12 months in both trials. The third trial recruited people with lumbar radicular pain (with or without low back pain) and disc herniation. Modic changes was not an inclusion criterion (population 4). This trial evaluated minocycline 100 mg versus amitriptyline 25 mg versus placebo and followed participants for 14 days (treatment duration). There were no trials with population 3. All three trials were at low risk of selection, performance, and detection bias. We rated one trial at high risk of attrition bias and unclear risk of reporting and other bias. The overall certainty of evidence is low to very low, primarily due to imprecision and indirectness. In people with low back pain, Modic type 1 changes, and disc herniation, the antibiotic oral amoxicillin (with or without clavulanate) may improve pain slightly and may result in a small to moderate improvement in disability at 12 to 14 weeks compared with placebo (low-certainty evidence, downgraded for imprecision and indirectness). At this time point, the mean back pain score was 50.6/100 (where a lower score indicates less pain) in the amoxicillin group versus 59/100 in the placebo group (mean difference (MD) -8.42 points, 95% CI -16.18 to -0.67; I² = 35%; 2 trials, 255 participants), and the mean disability score was 45.2/100 (where a lower score indicates less disability) in the amoxicillin group versus 55.7/100 in the placebo group (MD -10.52 points, 95% CI -15.94 to -5.09; I² = 0%; 2 trials, 255 participants). We are unsure if amoxicillin (with or without clavulanate) results in more people reporting adverse events (very low-certainty evidence, downgraded for imprecision, inconsistency, and indirectness). Adverse events were reported in 76 of every 100 people taking amoxicillin compared with 49 of every 100 people taking placebo (risk ratio (RR) 1.79, 95% CI 0.54 to 5.94; I² = 96%; 2 trials, 262 participants). We are unsure if amoxicillin (with or without clavulanate) results in more people reporting serious adverse events (very low-certainty evidence, downgraded for imprecision and indirectness). Serious adverse events were reported in three of every 100 people taking amoxicillin (with or without clavulanate) compared with two of every 100 people taking placebo (RR 1.43, 95% CI 0.11 to 18.35; I² = 45%; 2 trials, 262 participants). We are unsure of the effects of amoxicillin compared to placebo in people with low back pain, Modic type 2 change, and disc herniation. Similarly, we are unsure of the effects of minocycline compared to placebo or amitriptyline in people with low back pain, disc herniation, and no Modic changes. In people with low back pain, Modic type 1 changes, and evidence of disc herniation, the antibiotic amoxicillin (with or without clavulanate) may provide slight to small benefits in reducing back pain and small to moderate benefits in improving disability compared to placebo at 12 to 14 weeks. The evidence on the risk of adverse events, including serious adverse events, with amoxicillin (with or without clavulanate) is very uncertain. Further research is likely to change our confidence in the estimates. This review had no dedicated funding. Protocol (2021): DOI 10.1002/14651858.CD014221.

Background Opioids are commonly prescribed for acute pain. However, there is no overarching synthesis on their efficacy. Aim We set out to conduct an overview review of the efficacy and harms of opioid analgesics for acute pain. Methods Electronic databases were searched until 4 March 2025 without restriction for systematic reviews of randomised trials comparing opioids to placebo/no active treatment for any acute, non-malignant pain condition published since 2010. Screening, extraction and quality assessment were conducted independently by two authors. The primary outcome was pain. Secondary outcomes were adverse events. Data timepoints were immediate (≤ 3 h after administration—primary timepoint), short (> 3 to ≤ 6 h), intermediate (> 6 to ≤ 48 h) and long term (> 48 h). Random effect meta-analyses were conducted. AMSTAR 2 described review quality. Grading of Recommendations Assessment, Development and Evaluation determined evidence certainty. Results We included 59 reviews. There was high certainty some opioids (morphine, oxycodone, tramadol, papaveretum) reduced acute abdominal pain at immediate term (mean difference [MD] − 18.4, 95% CI − 31.9 to − 5.0) compared with placebo. However, there were no harms data. At immediate term, there was moderate certainty opioids reduced pain including dental surgery (MD − 19.5, 95% CI − 25.0 to − 14.0), and myringotomy (MD − 15.0, 95% CI − 19.6 to − 10.4). However, harms data were only available for dental surgery, finding no increased risk of adverse events. Oral opioids provided only very small pain relief for acute musculoskeletal pain at intermediate term (MD − 8.9, 95% CI − 13.5 to − 4.3; moderate certainty) but increased the risk of adverse events (risk difference [RD] 0.1, 95% CI 0.0 to 0.2; moderate certainty). Limitations Some opioids are not consistently efficacious across timepoints. Conclusions Opioid analgesics are efficacious in reducing pain in some acute conditions. Registration ROSPERO CRD42018109733.

There are few effective treatments for acute whiplash-associated disorder (WAD) following a road traffic crash. Early clinical features of central sensitis