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What are the effects of diagnostic labels and advice, and interactions between labels and advice, on perceived need for shoulder surgery for rotator cuff disease?2×2 factorial online randomised experiment.People with shoulder pain.Participants read a scenario describing a patient with rotator cuff disease and were randomised to bursitis label plus guideline-based advice, bursitis label plus treatment recommendation, rotator cuff tear label plus guideline-based advice, and rotator cuff tear label plus treatment recommendation. Guideline-based advice included encouragement to stay active and positive prognostic information. Treatment recommendation stressed that treatment is needed for recovery.Perceived need for surgery (primary outcome), imaging, an injection, a second opinion and to see a specialist; and perceived seriousness of the condition, recovery expectations, impact on work performance and need to avoid work.A total of 2,024 responses (99.8% of 2,028 randomised) were analysed. Labelling as bursitis (versus rotator cuff tear) decreased perceived need for surgery (mean effect -0.5 on a 0-to-10 scale, 98.3% CI -0.7 to -0.2), imaging and to see a specialist, and perceived seriousness of the condition and need to avoid work. Guideline-based advice (versus treatment recommendation) decreased perceived need for surgery (mean effect -1.0, 98.3% CI -1.3 to -0.7), imaging, an injection, a second opinion and to see a specialist, and perceived seriousness of the condition and recovery expectations. There was little to no evidence of an advice label interaction for any outcome.Labels and advice influenced perceived need for surgery and other secondary outcomes in people with rotator cuff disease, with larger effects for advice. There was evidence of little or no interaction between labels and advice for any outcome, but the additive effect of labels and advice appeared large for some outcomes (eg, perceived need for imaging and perceived seriousness of the condition).ACTRN12621001370897.

To evaluate the effects of a patient decision aid for people considering shoulder surgery.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.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.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.Research is needed to understand reasons for the lack of anticipated effects.Australia New Zealand Clinical Trials Registry (ACTRN12621000992808).

Background Patients presenting to Emergency Department (ED) with non-specific low back pain can receive more unnecessary, intensive and costly care than is recommended. The COVID-19 pandemic has provided an unprecedented opportunity to examine how health systems prioritise necessary care that provides clear benefits to patients. The purpose of this study was to examine the impact of COVID-19 on care of low back pain in the ED. Methods We performed a retrospective analysis of electronic medical record data on care for low back pain from three public hospitals in Sydney. We included patients diagnosed with spinal conditions who presented between March and May in 2019 and in 2020. Outcomes were the total number of patients presenting with spinal conditions to ED, the proportion diagnosed with non-specific low back pain, and the proportion receiving potentially unnecessary aspects of care (ambulance use, imaging, opioids, hospital admissions). We calculated relative risk with 95% CIs and examined plots with locally weighted smoothed curves. Results Presentations for spinal conditions over a three-month period to three EDs reduced from 694 in 2019 to 475 in 2020 (31% reduction, 95% CI = 26%–37%). The proportion of patients diagnosed with non-specific low back pain (83% in 2019 vs 86% in 2020), or receiving potentially unnecessary care were similar in 2019 and 2020 (Imaging = 25% vs 25%; Opioids = 54% vs 56%; Admitted = 18% vs 20%; pathology test = 24% vs 23%). The proportion of patients arriving by ambulance was higher during the pandemic; 29% in 2019 vs 41% in 2020 (RR = 1.39, 95% CI = 1.19–1.63). Conclusions ED presentations for low back pain associated with spinal conditions decreased substantially during the COVID-19 pandemic. Use of potentially unnecessary aspects of care did not change or increased during the pandemic.

Background Exercise for the prevention of low back pain recurrences is recommended, but under-researched. The effectiveness and cost-effectiveness of a walking program for preventing low back pain recurrence remains unknown. This a priori statistical analysis plan describes the methods of analysis for the WalkBack trial. Methods WalkBack is a prospectively registered, pragmatic, randomised controlled trial. The aim is to investigate the effectiveness and cost-effectiveness of a 6-month progressive and individualised walking and education program (intervention) for the prevention of low back pain recurrences, compared to a no-treatment control group. The primary outcome is days to the first recurrence of an episode of activity-limiting low back pain. Key secondary outcomes include days to any recurrence of low back pain, days to a care-seeking recurrence of low back pain, disability level, health-related quality of life, costs associated with low back pain and adverse events. All participants will be followed for a minimum of 12 months. Analysis will follow the intention-to-treat principle. Cox regression is planned to assess the effects for the outcomes of time to activity-limiting, minimal and care-seeking recurrence. Hazard ratios and median survival times with 95% confidence intervals will be calculated. The effect of the intervention on continuous outcomes will be estimated with repeated-measure linear mixed models. An economic evaluation will be performed from the societal perspective for recurrence prevented (yes/no) and quality-adjusted life years. The proportion of adverse events between groups will be compared using Fisher’s exact test. Discussion The WalkBack trial will provide evidence on the effectiveness and cost-effectiveness of a walking intervention to prevent low back pain recurrences. This statistical analysis plan provides transparency on the analysis of the trial. Trial registration WalkBack - Effectiveness and cost-effectiveness of a progressive individualised walking and education program for the prevention of a recurrence of low back pain. ACTRN12619001134112. Date Registered: 14/08/2019.

BackgroundUnderstanding barriers and enablers to monitoring and deprescribing opioids will enable the development of tailored interventions to improve both practices.ObjectiveTo perform a qualitative evidence synthesis of the barriers and enablers to monitoring ongoing appropriateness and deprescribing of opioids for chronic non-cancer pain (CNCP) and to map the findings to the Theoretical Domains Framework (TDF).MethodsWe included English-language qualitative studies that explored healthcare professional (HCP), patient, carer and the general public’s perceptions regarding monitoring and deprescribing opioids for CNCP. We searched MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED) and PsycINFO from inception to August 2020. Two authors independently selected the studies, extracted the data, assessed the methodological quality using the Critical Appraisal Skills Programme, and assessed the confidence in the findings using GRADE CERQual (Grading of Recommendations Assessment, Development, and Evaluation Confidence in the Evidence from Reviews of Qualitative Research). We used an inductive approach to synthesis of qualitative data and mapped identified themes to TDF domains.ResultsFrom 6948 records identified we included 21 studies, involving 209 HCPs and 330 patients. No studies involved carers or the general public. Five barrier themes were identified: limited alternatives to opioids, management of pain is top priority, patient understanding, expectations and experiences, prescriber pressures, and reluctance to change. Four enabler themes were identified: negative effects of opioids and benefits of deprescribing, clear communication and expectations for deprescribing, support for patients, and support for prescribers. 16 barrier and 12 enabler subthemes were identified; most were graded as high (n=15) or moderate (n=9) confidence. The TDF domains ‘beliefs about consequences’, ‘environmental context and resources’, ‘social influences’ and ‘emotion’ were salient for patients and HCPs. The domains ‘skills’ and ‘beliefs about capabilities’ were more salient for HCPs.ConclusionFuture implementation interventions aimed at monitoring and deprescribing opioids should target the patient and HCP barriers and enablers identified in this synthesis.PROSPERO registration numberCRD42019140784.

Objective To provide a comprehensive overview of the efficacy, safety, and tolerability of antidepressants for pain according to condition. Design Overview of systematic reviews. Data sources PubMed, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials from inception to 20 June 2022. Eligibility criteria for selecting studies Systematic reviews comparing any antidepressant with placebo for any pain condition in adults. Data extraction and synthesis Two reviewers independently extracted data. The main outcome measure was pain; for headache disorders it was frequency of headaches. Continuous pain outcomes were converted into a scale of 0 (no pain) to 100 (worst pain) and were presented as mean differences (95% confidence intervals). Dichotomous outcomes were presented as risk ratios (95% confidence intervals). Data were extracted from the time point closest to the end of treatment. When end of treatment was too variable across trials in a review, data were extracted from the outcome or time point with the largest number of trials and participants. Secondary outcomes were safety and tolerability (withdrawals because of adverse events). Findings were classified from each comparison as efficacious, not efficacious, or inconclusive. Certainty of evidence was assessed with the grading of recommendations assessment, development, and evaluation framework. Results 26 reviews (156 unique trials and >25 000 participants) were included. These reviews reported on the efficacy of eight antidepressant classes covering 22 pain conditions (42 distinct comparisons). No review provided high certainty evidence on the efficacy of antidepressants for pain for any condition. 11 comparisons (nine conditions) were found where antidepressants were efficacious, four with moderate certainty evidence: serotonin-norepinephrine reuptake inhibitors (SNRIs) for back pain (mean difference −5.3, 95% confidence interval −7.3 to −3.3), postoperative pain (−7.3, −12.9 to −1.7), neuropathic pain (−6.8, −8.7 to −4.8), and fibromyalgia (risk ratio 1.4, 95% confidence interval 1.3 to 1.6). For the other 31 comparisons, antidepressants were either not efficacious (five comparisons) or the evidence was inconclusive (26 comparisons). Conclusions Evidence of efficacy of antidepressants was found in 11 of the 42 comparisons included in this overview of systematic reviews—seven of the 11 comparisons investigated the efficacy of SNRIs. For the other 31 comparisons, antidepressants were either inefficacious or evidence on efficacy was inconclusive. The findings suggest that a more nuanced approach is needed when prescribing antidepressants for pain conditions. Systematic review registration PROSPERO CRD42022311073.

Objective To evaluate the comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain. Design Systematic review and network meta-analysis. Data sources Medline, PubMed, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and World Health Organization’s International Clinical Trials Registry Platform from database inception to 20 February 2022. Eligibility criteria for study selection Randomised controlled trials of analgesic medicines (eg, non-steroidal anti-inflammatory drugs, paracetamol, opioids, anti-convulsant drugs, skeletal muscle relaxants, or corticosteroids) compared with another analgesic medicine, placebo, or no treatment. Adults (≥18 years) who reported acute non-specific low back pain (for less than six weeks). Data extraction and synthesis Primary outcomes were low back pain intensity (0-100 scale) at end of treatment and safety (number of participants who reported any adverse event during treatment). Secondary outcomes were low back specific function, serious adverse events, and discontinuation from treatment. Two reviewers independently identified studies, extracted data, and assessed risk of bias. A random effects network meta-analysis was done and confidence was evaluated by the Confidence in Network Meta-Analysis method. Results 98 randomised controlled trials (15 134 participants, 49% women) included 69 different medicines or combinations. Low or very low confidence was noted in evidence for reduced pain intensity after treatment with tolperisone (mean difference −26.1 (95% confidence intervals −34.0 to −18.2)), aceclofenac plus tizanidine (−26.1 (−38.5 to −13.6)), pregabalin (−24.7 (−34.6 to −14.7)), and 14 other medicines compared with placebo. Low or very low confidence was noted for no difference between the effects of several of these medicines. Increased adverse events had moderate to very low confidence with tramadol (risk ratio 2.6 (95% confidence interval 1.5 to 4.5)), paracetamol plus sustained release tramadol (2.4 (1.5 to 3.8)), baclofen (2.3 (1.5 to 3.4)), and paracetamol plus tramadol (2.1 (1.3 to 3.4)) compared with placebo. These medicines could increase the risk of adverse events compared with other medicines with moderate to low confidence. Moderate to low confidence was also noted for secondary outcomes and secondary analysis of medicine classes. Conclusions The comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain are uncertain. Until higher quality randomised controlled trials of head-to-head comparisons are published, clinicians and patients are recommended to take a cautious approach to manage acute non-specific low back pain with analgesic medicines. Systematic review registration PROSPERO CRD42019145257

BACKGROUND: Pharmacological interventions are the most used treatment for low back pain (LBP). Use of evidence from systematic reviews of the effects of pharmacological interventions for LBP published in the Cochrane Library, is limited by lack of a comprehensive overview.OBJECTIVES: To summarise the evidence from Cochrane Reviews of the efficacy, effectiveness, and safety of systemic pharmacological interventions for adults with non-specific LBP.METHODS: The Cochrane Database of Systematic Reviews was searched from inception to 3 June 2021, to identify reviews of randomised controlled trials (RCTs) that investigated systemic pharmacological interventions for adults with non-specific LBP. Two authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools. The review focused on placebo comparisons and the main outcomes were pain intensity, function, and safety.MAIN RESULTS: Seven Cochrane Reviews that included 103 studies (22,238 participants) were included. There is high confidence in the findings of five reviews, moderate confidence in one, and low confidence in the findings of another. The reviews reported data on six medicines or medicine classes: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, benzodiazepines, opioids, and antidepressants. Three reviews included participants with acute or sub-acute LBP and five reviews included participants with chronic LBP. Acute LBP Paracetamol There was high-certainty evidence for no evidence of difference between paracetamol and placebo for reducing pain intensity (MD 0.49 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -1.99 to 2.97), reducing disability (MD 0.05 on a 0 to 24 scale (higher scores indicate worse disability), 95% CI -0.50 to 0.60), and increasing the risk of adverse events (RR 1.07, 95% CI 0.86 to 1.33). NSAIDs There was moderate-certainty evidence for a small between-group difference favouring NSAIDs compared to placebo at reducing pain intensity (MD -7.29 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -10.98 to -3.61), high-certainty evidence for a small between-group difference for reducing disability (MD -2.02 on a 0-24 scale (higher scores indicate worse disability), 95% CI -2.89 to -1.15), and very low-certainty evidence for no evidence of an increased risk of adverse events (RR 0.86, 95% CI 0. 63 to 1.18). Muscle relaxants and benzodiazepines There was moderate-certainty evidence for a small between-group difference favouring muscle relaxants compared to placebo for a higher chance of pain relief (RR 0.58, 95% CI 0.45 to 0.76), and higher chance of improving physical function (RR 0.55, 95% CI 0.40 to 0.77), and increased risk of adverse events (RR 1.50, 95% CI 1. 14 to 1.98). Opioids None of the included Cochrane Reviews aimed to identify evidence for acute LBP. Antidepressants No evidence was identified by the included reviews for acute LBP. Chronic LBP Paracetamol No evidence was identified by the included reviews for chronic LBP. NSAIDs There was low-certainty evidence for a small between-group difference favouring NSAIDs compared to placebo for reducing pain intensity (MD -6.97 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -10.74 to -3.19), reducing disability (MD -0.85 on a 0-24 scale (higher scores indicate worse disability), 95% CI -1.30 to -0.40), and no evidence of an increased risk of adverse events (RR 1.04, 95% CI -0.92 to 1.17), all at intermediate-term follow-up (> 3 months and ≤ 12 months postintervention). Muscle relaxants and benzodiazepines There was low-certainty evidence for a small between-group difference favouring benzodiazepines compared to placebo for a higher chance of pain relief (RR 0.71, 95% CI 0.54 to 0.93), and low-certainty evidence for no evidence of difference between muscle relaxants and placebo in the risk of adverse events (RR 1.02, 95% CI 0.67 to 1.57). Opioids There was high-certainty evidence for a small between-group difference favouring tapentadol compared to placebo at reducing pain intensity (MD -8.00 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -1.22 to -0.38), moderate-certainty evidence for a small between-group difference favouring strong opioids for reducing pain intensity (SMD -0.43, 95% CI -0.52 to -0.33), low-certainty evidence for a medium between-group difference favouring tramadol for reducing pain intensity (SMD -0.55, 95% CI -0.66 to -0.44) and very low-certainty evidence for a small between-group difference favouring buprenorphine for reducing pain intensity (SMD -0.41, 95% CI -0.57 to -0.26). There was moderate-certainty evidence for a small between-group difference favouring strong opioids compared to placebo for reducing disability (SMD -0.26, 95% CI -0.37 to -0.15), moderate-certainty evidence for a small between-group difference favouring tramadol for reducing disability (SMD -0.18, 95% CI -0.29 to -0.07), and low-certainty evidence for a small between-group difference favouring buprenorphine for reducing disability (SMD -0.14, 95% CI -0.53 to -0.25). There was low-certainty evidence for a small between-group difference for an increased risk of adverse events for opioids (all types) compared to placebo; nausea (RD 0.10, 95% CI 0.07 to 0.14), headaches (RD 0.03, 95% CI 0.01 to 0.05), constipation (RD 0.07, 95% CI 0.04 to 0.11), and dizziness (RD 0.08, 95% CI 0.05 to 0.11). Antidepressants There was low-certainty evidence for no evidence of difference for antidepressants (all types) compared to placebo for reducing pain intensity (SMD -0.04, 95% CI -0.25 to 0.17) and reducing disability (SMD -0.06, 95% CI -0.40 to 0.29).AUTHORS' CONCLUSIONS: We found no high- or moderate-certainty evidence that any investigated pharmacological intervention provided a large or medium effect on pain intensity for acute or chronic LBP compared to placebo. For acute LBP, we found moderate-certainty evidence that NSAIDs and muscle relaxants may provide a small effect on pain, and high-certainty evidence for no evidence of difference between paracetamol and placebo. For safety, we found very low- and high-certainty evidence for no evidence of difference with NSAIDs and paracetamol compared to placebo for the risk of adverse events, and moderate-certainty evidence that muscle relaxants may increase the risk of adverse events. For chronic LBP, we found low-certainty evidence that NSAIDs and very low- to high-certainty evidence that opioids may provide a small effect on pain. For safety, we found low-certainty evidence for no evidence of difference between NSAIDs and placebo for the risk of adverse events, and low-certainty evidence that opioids may increase the risk of adverse events.

Objectives To investigate whether intensive supervised rehabilitation following ACL reconstruction leads to superior self-reported function and sports participation compared to less supervised rehabilitation. Design Systematic review and meta-analysis. Methods We included randomised controlled trials (RCTs) comparing supervised rehabilitation to rehabilitation with a similar protocol that used less supervised sessions for athletes following ACL reconstruction. Two reviewers independently screened studies and extracted data. The Physiotherapy Evidence Database (PEDro) scale was used to evaluate methodological quality and GRADE to evaluate overall quality of evidence. Self-reported function and sports participation were the primary outcomes. Data were pooled using random effects meta-analyses. Results Our search retrieved 4075 articles. Seven articles reporting on six RCTs were included (n = 353). Very-low to low-certainty evidence suggests intensive supervised rehabilitation is not superior to less supervised rehabilitation following ACL reconstruction for improving self-reported function, sports participation, knee flexor and extensor strength, range of motion, sagittal plane knee laxity, single leg hop performance, or quality of life. Conclusion Based on uncertain evidence, intensive supervised rehabilitation is not superior to less supervised rehabilitation for athletes following ACL reconstruction. Although high-quality RCTs are needed to provide more certain evidence, clinicians should engage athletes in shared decision making to ensure athletes’ rehabilitation decisions align with current evidence on supervised rehabilitation as well as their preferences and values.

Aim Aurora kinase A (AURKA) is a pleiotropic serine/threonine kinase that orchestrates mitotic progression. Paclitaxel stabilises microtubules and disrupts mitotic spindle assembly. The combination of AURKA inhibitor (alisertib) plus paclitaxel may be synergistic in rapidly proliferative cancers. We evaluated the safety and maximum tolerated dose (MTD) of alisertib in combination with nab-paclitaxel and its preliminary efficacy in patients with refractory high-grade neuroendocrine tumours (NETs). Method This is a two-part, Phase 1 study. In Part A (dose escalation), a standard 3 + 3 design was used to determine MTD. In Part B (dose expansion), patients with predominantly refractory high-grade NETs were enrolled. Results In total, 31 patients were enrolled and treated (16 in Part A and 15 in Part B). The MTD of alisertib was 40 mg BID on D1-3 per week and nab-paclitaxel 100mg/m2 weekly: 3 weeks, 1 week off. Dose-limiting toxicity was neutropenia, and other common side-effects included fatigue, mucositis, and diarrhoea. In Part A, a patient with small-cell lung cancer with partial response (PR) was treated for more than 2 years, whereas four other patients with pancreatic ductal adenocarcinoma (one patient), small cell lung cancer (SCLC) (two patients), or high-grade NET (one patient) achieved stable disease (SD). In Part B, 13 of 15 enrolled patients had high-grade NETs. Of these, one had PR, and four had SD for more than 10 months. Conclusions The combination of alisertib and nab-paclitaxel has manageable side-effect profile and showed promising preliminary efficacy in high-grade NETs, warranting further testing. Trial registration ClinicalTrials.gov identifier: NCT01677559 .

The study aimed to determine how much change in neurogenic claudication spinal surgeons expect in patients following lumbar decompression for lumbar spine stenosis (LSS), and radicular leg pain following microdiscectomy. Secondary aims were to identify surgeons’ preferences regarding surgical techniques for lumbar decompression, and their rating of the quality of current evidence for lumbar decompression. All Australian spine surgeons were invited, of whom 71 completed the survey (31% response rate). Only registered spinal surgeons were included. The online survey, administered using REDCap, included 4 sections: demographics and background; expected change in symptoms on a +/− 100% scale (−100% worst, 0% no change and 100% best possible); surgical preference; and rating of current evidence for lumbar decompression compared with other treatments. There were 71 complete responses, 76% were neurosurgeons (N = 54), predominantly male (96%; N = 68). On average, surgeons expected an 86% (median: 87%, inter-quartile range (IQR): 80%, 91%) improvement in neurogenic claudication following lumbar decompression for LSS and 89% (median: 91%, IQR: 85%, 95%) improvement in radicular pain following microdiscectomy. A multiple linear regression found no surgeon characteristics were associated with expected change following surgery. The preferred surgical technique for LSS was full laminectomy (58%; N = 41). Thirty-five percent of surgeons accurately rated the evidence supporting the superiority of lumbar decompression compared with non-surgical care for LSS as low quality. Spine surgeons expect large symptom improvements following lumbar decompression and microdiscectomy. Understanding of the current evidence was higher for lumbar decompression with fusion, than for decompression alone for LSS.

Objective To investigate what format for providing patient information (i.e. written summary, infographic or video animation) is most effective for promoting correct beliefs about imaging and inevitable consequences of low back pain (LBP). Design Randomised controlled trial. Setting/Patients One hundred and fifty-nine patients with non-specific LBP were recruited from outpatient physiotherapy clinics. Intervention Participants were randomised to receive patient information in one of three formats: video animation, infographic or written summary. Patients were allowed to read or watch the materials for up to 20 min. Measurements Outcome were assessed before and immediately after the intervention. The primary outcome was the Back Beliefs Questionnaire. The secondary outcome was beliefs about imaging for LBP assessed by two questions. Results All 159 patients completed the study. Our findings revealed no difference between groups for the Back Beliefs Questionnaire. Correct beliefs about imaging were more likely with the infographic than the video animation (Question 1- Odds Ratio [OR] = 3.9, 95% confidence interval [CI]: 1.7, 8.7; Question 2- OR = 6.8, 95%CI: 2.7, 17.2) and more likely with the written summary than the video animation (Question 1- OR = 3.3, 95%CI: 1.5, 7.4; Question 2- OR = 3.7, 95%CI: 1.6, 8.5). No difference between infographic and written summary formats were reported for the questions assessing LBP imaging beliefs. Conclusion The three materials were equally effective in improving patient's general beliefs about LBP care. However, the traditional written summary or infographic formats were more effective than the video animation format for improving beliefs about imaging for LBP.

Background The importance of lumbar findings on magnetic resonance imaging (MRI) remains controversial. Changes in lumbar MRI findings over time may provide important insights into the causes of low back pain. However, the reliability and validity of temporal changes are unknown. Objective To (1) investigate the interrater reliability of subjective radiologist reporting of temporal changes in lumbar spine MRI findings and (2) determine how commonly temporal changes are reported when two scans are conducted 30 minutes apart (considered false positives). Design Cross-sectional study. Setting Radiology clinic. Participants Forty volunteers (mean age 40; 53% female) with current (n = 31) or previous (n = 9) low back pain underwent initial lumbar MRI on a single 3T scanner. Participants then lay on a bed for 30 minutes before undergoing an identical MRI. In addition, we purposely selected five participants from a previous study with repeat lumbar MRI scans where temporal changes were reported in at least one MRI finding (1-12 weeks after initial scan) and another five participants where no temporal change was reported. The 10 participants were included in analyses for aim 1 only. Interventions Not applicable. Main outcome measures Two blinded radiologists reported on temporal changes between the baseline and repeat scan for 12 different MRI findings (eg, disk herniation, annular fissure) at five levels. Results The interrater reliability of subjective reporting of temporal changes was poor for all MRI findings based on Kappa values (≤ 0.24), but agreement was relatively high (≥ 90.8%). This is explained by the low prevalence of temporal changes as demonstrated by high values for Prevalence and Bias Adjusted Kappa (≥ 0.82). "False positive" temporal changes were reported by at least one radiologist for most MRI findings, but the rate was generally low. Conclusions Caution is required when interpreting temporal changes in lumbar MRI findings owing to low reliability and some false positive reporting.

The comparative benefits and harms of opioids for musculoskeletal pain in the emergency department (ED) are uncertain.To evaluate the comparative effectiveness and harms of opioids for musculoskeletal pain in the ED setting.Electronic databases and registries from inception to 7 February 2022.Randomized controlled trials of any opioid analgesic compared with placebo or a nonopioid analgesic administered or prescribed to adults in or on discharge from the ED.Pain and disability were rated on a scale of 0 to 100 and pooled using a random-effects model. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework.Forty-two articles were included (Low or very low GRADE ratings for some outcomes, unexplained heterogeneity, and little information on long-term outcomes.The risk-benefit balance of opioids versus placebo, paracetamol, NSAIDs, and local or systemic anesthetics is uncertain. Opioids may have equivalent pain outcomes compared with NSAIDs, but evidence on comparisons of harms is very uncertain and heterogeneous. Although factors such as route of administration or dosage may explain some heterogeneity, more work is needed to identify which subgroups will have a more favorable benefit-risk balance for one analgesic over another. Longer-term pain management once dose thresholds are reached is also uncertain.None. (PROSPERO: CRD42021275293).

IMPORTANCE: Audit and feedback can improve professional practice, but few trials have evaluated its effectiveness in reducing potential overuse of musculoskeletal diagnostic imaging in general practice. OBJECTIVE: To evaluate the effectiveness of audit and feedback for reducing musculoskeletal imaging by high-requesting Australian general practitioners (GPs). DESIGN, SETTING, AND PARTICIPANTS: This factorial cluster-randomized clinical trial included 2271 general practices with at least 1 GP who was in the top 20% of referrers for 11 imaging tests (of the lumbosacral or cervical spine, shoulder, hip, knee, and ankle/hind foot) and for at least 4 individual tests between January and December 2018. Only high-requesting GPs within participating practices were included. The trial was conducted between November 2019 and May 2021, with final follow-up on May 8, 2021. INTERVENTIONS: Eligible practices were randomized in a 1:1:1:1:1 ratio to 1 of 4 different individualized written audit and feedback interventions (n = 3055 GPs) that varied factorially by (1) frequency of feedback (once vs twice) and (2) visual display (standard vs enhanced display highlighting highly requested tests) or to a control condition of no intervention (n = 764 GPs). Participants were not masked. MAIN OUTCOMES AND MEASURES: The primary outcome was the overall rate of requests for the 11 targeted imaging tests per 1000 patient consultations over 12 months, assessed using routinely collected administrative data. Primary analyses included all randomized GPs who had at least 1 patient consultation during the study period and were performed by statisticians masked to group allocation. RESULTS: A total of 3819 high-requesting GPs from 2271 practices were randomized, and 3660 GPs (95.8%; n = 727 control, n = 2933 intervention) were included in the primary analysis. Audit and feedback led to a statistically significant reduction in the overall rate of imaging requests per 1000 consultations compared with control over 12 months (adjusted mean, 27.7 [95% CI, 27.5-28.0] vs 30.4 [95% CI, 29.8-30.9], respectively; adjusted mean difference, −2.66 [95% CI, −3.24 to −2.07]; P

To investigate whether different labels for rotator cuff disease influence people's perceived need for surgery.Randomized controlled experiment.Participants with and without shoulder pain read a vignette describing a patient with rotator cuff disease and were randomized to 1 of 6 terms describing rotator cuff disease:One thousand three hundred eight (80% of 1626) responses were analyzed. Participants' mean ± SD age was 40.3 ± 16.0 years, and 59% were women. Mean perceived need for surgery (0-10 scale) was low and slightly higher among those assigned to the rotator cuff tear label compared to the bursitis label (2.6 versus 2.1; adjusted mean difference, 0.7; 99.67% CI: 0.0, 1.4). Mean perceived need for imaging (0-10) was moderate and slightly higher among those assigned to the rotator cuff tear (4.7 versus 3.7; adjusted mean difference, 1.0; 99.67% CI: 0.2, 1.9) and subacromial impingement syndrome labels (4.7 versus 3.7; adjusted mean difference, 1.0; 99.7% CI: 0.1, 1.9) compared to the bursitis label.There were small differences in the perceived need for surgery and imaging between some labels, which could be important at the population level.

Background Abstracts of systematic reviews (SR) are frequently used to guide clinical decision-making. However, if the abstract is inadequately reported, key information may be missing and it may not accurately summarize the results of the review. Objective We aimed to investigate 1) if abstracts are fully reported; 2) if abstract reporting is associated with review/journal characteristics in physical therapy for low back pain (LBP); and 3) if these abstracts are consistent with the corresponding full texts. Methods We searched the Physiotherapy Evidence Database for SRs in physical therapy for LBP published between 2015 and 2017. Associations between abstract reporting quality and review/journal characteristics were explored with linear regression. Abstract reporting was assessed with the 12 item Preferred Reporting Items for Systematic Reviews and Meta-Analyses for abstracts (PRISMA-A) checklist. Consistency of reporting between abstracts and the full text was evaluated by comparing responses to each item of the PRISMA-A using Kappa coefficients. Methodological quality of the reviews was assessed with A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2). Results We included 66 SRs, 9 Cochrane and 57 non-Cochrane. Review methodological quality ranged from ‘high’ (8%) to ‘critically low’ (76%). The mean ± SD of the “total number of PRISMA-A fully reported items” (range 0–12 points for fully reported items) was 4.1 ± 1.9 points for non-Cochrane review abstracts and 9.9 ± 1.1 points for Cochrane abstracts. Factors associated with reporting quality of abstracts were: journal impact factor (s 0.20; 95% CI: 0.06, 0.35), number of words in abstract (s 0.01; 95% CI: 0.00, 0.01) and review methodological quality (‘critically low’ with s −3.06; 95% CI: −5.30, −0.82; with ‘high’ as reference variable). There was typically inconsistent reporting between abstract and full text, with most Kappa values lower than 0.60. Conclusions The abstracts of SRs in physical therapy for LBP were poorly reported and inconsistent with the full text. The reporting quality of abstracts was higher in journals with a higher impact factor, in abstracts with a greater number of words, and when the review was of higher methodological quality.

Background Community awareness of the harms of overdiagnosis remains low. Objective To evaluate community responses to a public health campaign designed for health service waiting rooms that focuses on the harms of unnecessary diagnostic imaging for low back pain. Methods We conducted two focus groups of 19 community members with or without low back pain in Sydney, Australia. This study formed the fourth and final stage of the development process of a public health campaign: (a) initial design, (b) expert review and revision, (c) online experiment and (d) community views & revision. We evaluated reactions to components of the campaign that included digital posters and an information leaflet using strong imagery and messaging about the risk of overdiagnosis. We conducted a qualitative thematic analysis to identify main themes. Results Community members reacted with surprise, initial mistrust, and occasionally anger towards imagery and messaging that suggested diagnostic imaging tests could be unnecessary and harmful. With further reflection and discussion, and after reading longer format information about overdiagnosis, the participants found some of the messages informative and useful. Participants appeared to gain a better understanding of the concept of overdiagnosis and the importance of not rushing to imaging. Conclusions Public health campaigns including posters and leaflets displayed in waiting rooms could raise awareness about overuse of diagnostic imaging and the harms of overdiagnosis more broadly. However, negative reactions are possible and must be managed carefully. Patient or public contribution We involved a community participation manager who provided advice on the focus group discussion guide, participant recruitment and manuscript presentation.

Purpose: To estimate the healthcare resource utilisation of an Australian cohort of people with sciatica and explore individual-level factors associated with expenditure. Methods: Healthcare utilisation (services and medication) data from a randomised, double-blind, placebo-controlled trial of pregabalin in patients with sciatica (n = 185) were analysed to estimate healthcare expenditure of participants over 12 months. Associations between key baseline socio-economic, pain and quality of life characteristics and healthcare expenditure were examined using generalised linear imputation models. Results: On average, participants accessed AUD$1,134 of healthcare over the year, predominantly made up of $114 of medication and $914 of health services, which included $418 of physiotherapy services. Participants randomised to receive pregabalin incurred higher expenditure ($1,263 compared to $1,001 for placebo), which was largely driven by pregabalin ($158) and greater health services ($107). Healthcare expenditure was significantly higher for participants prescribed pregabalin, earning greater than $1,700 per week ($88,400 per year) and reporting poorer quality of life (physical and mental). Conclusion: Our results suggest inefficiency in the use of healthcare resources due to increased healthcare resource utilisation in people with sciatica treated with pregabalin, compared to placebo. Costs of treating sciatica varied based on individual quality of life and socio-economic characteristics.

Objective To evaluate the efficacy and safety of paracetamol as an analgesic medication in a range of painful conditions. Study design Systematic review of systematic reviews of the analgesic effects of paracetamol in randomised, placebo-controlled trials. Conduct of systematic reviews was assessed with AMSTAR-2; confidence in effect estimates (quality of evidence) was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Data sources MEDLINE, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews; systematic reviews published 1 January 2010 - 30 April 2020. Data synthesis We extracted pain and adverse events outcomes from 36 systematic reviews that assessed the efficacy of paracetamol in 44 painful conditions. Continuous pain outcomes were expressed as mean differences (MDs; standardised 0-10-point scale); dichotomous outcomes were expressed as risk ratios (RRs). There is high quality evidence that paracetamol provides modest pain relief for people with knee or hip osteoarthritis (MD, -0.3 points; 95% CI, -0.6 to -0.1 points) and after craniotomy (MD, -0.8 points; 95% CI, -1.4 to -0.2 points); there is moderate quality evidence for its efficacy in tension-type headache (pain-free at 2 hours: RR, 1.3; 95% CI, 1.1-1.4) and perineal pain soon after childbirth (patients experiencing 50% pain relief: RR, 2.4; 95% CI, 1.5-3.8). There is high quality evidence that paracetamol is not effective for relieving acute low back pain (MD, 0.2 points; 95% CI, -0.1 to 0.4 points). Evidence regarding efficacy in other conditions was of low or very low quality. Frequency of adverse events was generally similar for people receiving placebo or paracetamol, except that transient elevation of blood liver enzyme levels was more frequent during repeated administration of paracetamol to patients with spinal pain (RR, 3.8; 95% CI, 1.9-7.4). Conclusions For most conditions, evidence regarding the effectiveness of paracetamol is insufficient for drawing firm conclusions. Evidence for its efficacy in four conditions was moderate to strong, and there is strong evidence that paracetamol is not effective for reducing acute low back pain. Investigations that evaluate more typical dosing regimens are required. Prospero registration CRD42015029282 (prospective).

Breast cancer bone metastases are common and incurable. Tumoral integrin β3 (β3) expression is induced through interaction with the bone microenvironment. Although β3 is known to promote bone colonization, its functional role during therapy of established bone metastases is not known. We found increased numbers of β3+ tumor cells in murine bone metastases after docetaxel chemotherapy. β3+ tumor cells were present in 97% of post-neoadjuvant chemotherapy triple-negative breast cancer patient samples (n = 38). High tumoral β3 expression was associated with worse outcomes in both pre- and postchemotherapy triple-negative breast cancer groups. Genetic deletion of tumoral β3 had minimal effect in vitro, but significantly enhanced in vivo docetaxel activity, particularly in the bone. Rescue experiments confirmed that this effect required intact β3 signaling. Ultrastructural, transcriptomic, and functional analyses revealed an alternative metabolic response to chemotherapy in β3-expressing cells characterized by enhanced oxygen consumption, reactive oxygen species generation, and protein production. We identified mTORC1 as a candidate for therapeutic targeting of this β3-mediated, chemotherapy-induced metabolic response. mTORC1 inhibition in combination with docetaxel synergistically attenuated murine bone metastases. Furthermore, micelle nanoparticle delivery of mTORC1 inhibitor to cells expressing activated αvβ3 integrins enhanced docetaxel efficacy in bone metastases. Taken together, we show that β3 integrin induction by the bone microenvironment promotes resistance to chemotherapy through an altered metabolic response that can be defused by combination with αvβ3-targeted mTORC1 inhibitor nanotherapy. Our work demonstrates the importance of the metastatic microenvironment when designing treatments and presents new, bone-specific strategies for enhancing chemotherapeutic efficacy.

OBJECTIVE: The aim of the review was to appraise clinical practice guidelines and their recommendations for the treatment of lumbar spinal stenosis.METHODS: PubMed, Medline, CINAHL, Embase, and Cochrane Central Register of Controlled Trials were searched up until 25/01/2020 for clinical practice guidelines on the management of lumbar spinal stenosis with a systematic process to generate recommendations and were publicly available.RESULTS: Ten guidelines were included, with a total of 76 recommendations for the treatment of lumbar spinal stenosis. Only 4 of the 10 guidelines were of satisfactory methodological quality according to the AGREE II instrument. Around three-quarters of recommendations (72.4%) were presented with poor evidence, with the remaining 21 presenting (27.6%) fair evidence. No recommendation presented good evidence. Recommendations were made on four types of interventions: surgery, injections, medications, and other nonsurgical treatments, with supporting evidence similar for all four treatment types. Positive recommendations were more common for injections (12/13=92.3%) and surgery (10/15=66%) than for nonsurgical treatments (6/21=28.6%) or medications (1/27=3.75%).CONCLUSIONS: Ten guidelines on the management of lumbar spinal stenosis were identified in the systematic review, but only four were of adequate methodological quality. While the evidence underpinning the various types of interventions was similar, guidelines tended to endorse surgery and injections but not nonsurgical interventions and medicines. These results support the need for greater rigor and inclusion of steps to minimize bias in the production of guidelines.

ObjectivesTo explore how people perceive different advice for rotator cuff disease in terms of words/feelings evoked by the advice and treatment needs.SettingWe performed a content analysis of qualitative data collected in a randomised experiment.Participants2028 people with shoulder pain read a vignette describing someone with rotator cuff disease and were randomised to:bursitis labelplusguideline-based advice, bursitis labelplustreatment recommendation, rotator cuff tear labelplusguideline-based adviceandrotator cuff tear labelplustreatment recommendation. Guideline-based adviceincluded encouragement to stay active and positive prognostic information.Treatment recommendationemphasised that treatment is needed for recovery.Primary and secondary outcomesParticipants answered questions about: (1) words/feelings evoked by the advice; (2) treatments they feel are needed. Two researchers developed coding frameworks to analyse responses.Results1981 (97% of 2039 randomised) responses for each question were analysed.Guideline-based advice(vstreatment recommendation) more often elicited words/feelings of reassurance, having a minor issue, trust in expertise and feeling dismissed, and treatment needs of rest, activity modification, medication, wait and see, exercise and normal movements.Treatment recommendation(vsguideline-based advice) more often elicited words/feelings of needing treatment/investigation, psychological distress and having a serious issue, and treatment needs of injections, surgery, investigations, and to see a doctor.ConclusionsWords/feelings evoked by advice for rotator cuff disease and perceived treatment needs may explain whyguideline-based advicereduces perceived need for unnecessary care compared to atreatment recommendation.

Amiri et al1provide extensive burden of disease estimates for gout in the Middle East and North Africa (MENA) region sourced from the Global Burden of Disease (GBD) 2019 study. We would like to draw attention to the considerable uncertainty with these estimates and advise readers to interpret the estimates cautiously.

ObjectivesTo determine the proportion of low back pain presentations that are admitted to hospital from the emergency department (ED), the proportion of hospital admissions due to a primary diagnosis of low back pain and the mean hospital length of stay (LOS), globally.MethodsWe searched MEDLINE, CINAHL, EMBASE, Web of Science, PsycINFO and LILACS from inception to July 2022. Secondary data were retrieved from publicly available government agency publications and international databases. Studies investigating admitted patients aged >18 years with a primary diagnosis of musculoskeletal low back pain and/or lumbosacral radicular pain were included.ResultsThere was high heterogeneity in admission rates for low back pain from the ED, with a median of 9.6% (IQR 3.3–25.2; 9 countries). The median percentage of all hospital admissions that were due to low back pain was 0.9% (IQR 0.6–1.5; 30 countries). The median hospital LOS across 39 countries was 6.2 days for ‘dorsalgia’ (IQR 4.4–8.6) and 5.4 days for ‘intervertebral disc disorders’ (IQR 4.1–8.4). Low back pain admissions per 100 000 population had a median of 159.1 (IQR 82.6–313.8). The overall quality of the evidence was moderate.ConclusionThis is the first systematic review with meta-analysis summarising the global prevalence of hospital admissions and hospital LOS for low back pain. There was relatively sparse data from rural and regional regions and low-income countries, as well as high heterogeneity in the results.

Objective To describe the proportion of national health surveys that contain questions on the prevalence and consequences of musculoskeletal conditions. Methods We used a comprehensive search strategy to obtain national health surveys from the 218 countries listed by the World Bank. Two authors independently extracted information from each national health survey. Outcomes were the proportion of surveys that contained questions on the prevalence of musculoskeletal conditions using the Global Burden of Disease categorization of RA, OA, low back pain, neck pain, gout and other and contained condition-specific questions about activity limitation, severity of pain and work absence. We also measured how frequently the prevalence of low back pain was measured using a consensus-based standard definition for low back pain prevalence studies. Results We identified national health surveys from 170 countries. Sixty-two (36.4%), the majority from high-income countries (n = 43), measured the prevalence of at least one musculoskeletal condition. OA [53 (85.4%)], low back pain [39 (62.9%)] and neck pain [37 (59.7%)] were most commonly measured, while RA and gout prevalence were only measured in 10 (5.9%) and 3 (1.8%) surveys, respectively. A minority of surveys assessed condition-specific activity limitations [6 (3.6%)], pain severity [5 (2.9%)] and work absence [1 (0.6%)]. Only one survey used the consensus-based standard definition for low back pain. Conclusion Musculoskeletal conditions are neglected in the majority of national health surveys. Monitoring musculoskeletal conditions through ongoing surveys is crucial for the development and evaluation of health policies to reduce their burden.