Search

Background Antidepressant medicines are used to manage symptoms of low back pain. The efficacy, acceptability, and safety of antidepressant medicines for low back pain (LBP) are not clear. We aimed to evaluate the efficacy, acceptability, and safety of antidepressant medicines for LBP. Methods We searched CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, the EU Clinical Trials Register, and the WHO International Clinical Trial Registry Platform from inception to May 2020. We included published and trial registry reports of RCTs that allocated adult participants with LBP to receive an antidepressant medicine or a placebo medicine. Pairs of authors independently extracted data in duplicate. We extracted participant characteristics, study sample size, outcome values, and measures of variance for each outcome. We data using random-effects meta-analysis models and calculated estimates of effects and heterogeneity for each outcome. We formed judgments of confidence in the evidence in accordance with GRADE. We report our findings in accordance with the PRISMA statement. We prespecified all outcomes in a prospectively registered protocol. The primary outcomes were pain intensity and acceptability. We measured pain intensity at end-of-treatment on a 0–100 point scale and considered 10 points the minimal clinically important difference. We defined acceptability as the odds of stopping treatment for any reason. Results We included 23 RCTs in this review. Data were available for pain in 17 trials and acceptability in 14 trials. Treatment with antidepressants decreased pain intensity by 4.33 points (95% CI − 6.15 to − 2.50) on a 0–100 scale, compared to placebo. Treatment with antidepressants increased the odds of stopping treatment for any reason (OR 1.27 [95% CI 1.03 to 1.56]), compared to placebo. Conclusions Treatment of LBP with antidepressants is associated with small reductions in pain intensity and increased odds of stopping treatment for any reason, compared to placebo. The effect on pain is not clinically important. The effect on acceptability warrants consideration. These findings provide Level I evidence to guide clinicians in their use of antidepressants to treat LBP. Trial registration We prospectively registered the protocol for this systematic review on PROSPERO (CRD42020149275).

Objective To investigate the efficacy, acceptability, and safety of muscle relaxants for low back pain. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and WHO ICTRP from inception to 23 February 2021. Eligibility criteria for study selection Randomised controlled trials of muscle relaxants compared with placebo, usual care, waiting list, or no treatment in adults (≥18 years) reporting non-specific low back pain. Data extraction and synthesis Two reviewers independently identified studies, extracted data, and assessed the risk of bias and certainty of the evidence using the Cochrane risk-of-bias tool and Grading of Recommendations, Assessment, Development and Evaluations, respectively. Random effects meta-analytical models through restricted maximum likelihood estimation were used to estimate pooled effects and corresponding 95% confidence intervals. Outcomes included pain intensity (measured on a 0-100 point scale), disability (0-100 point scale), acceptability (discontinuation of the drug for any reason during treatment), and safety (adverse events, serious adverse events, and number of participants who withdrew from the trial because of an adverse event). Results 49 trials were included in the review, of which 31, sampling 6505 participants, were quantitatively analysed. For acute low back pain, very low certainty evidence showed that at two weeks or less non-benzodiazepine antispasmodics were associated with a reduction in pain intensity compared with control (mean difference −7.7, 95% confidence interval−12.1 to−3.3) but not a reduction in disability (−3.3, −7.3 to 0.7). Low and very low certainty evidence showed that non-benzodiazepine antispasmodics might increase the risk of an adverse event (relative risk 1.6, 1.2 to 2.0) and might have little to no effect on acceptability (0.8, 0.6 to 1.1) compared with control for acute low back pain, respectively. The number of trials investigating other muscle relaxants and different durations of low back pain were small and the certainty of evidence was reduced because most trials were at high risk of bias. Conclusions Considerable uncertainty exists about the clinical efficacy and safety of muscle relaxants. Very low and low certainty evidence shows that non-benzodiazepine antispasmodics might provide small but not clinically important reductions in pain intensity at or before two weeks and might increase the risk of an adverse event in acute low back pain, respectively. Large, high quality, placebo controlled trials are urgently needed to resolve uncertainty. Systematic review registration PROSPERO CRD42019126820 and Open Science Framework https://osf.io/mu2f5/ .

Background Chronic low back pain (CLBP) is a global health problem associated with an increasing burden on individuals, health care systems, and society. Common treatments for people with CLBP produce, on average, small short-term improvements in pain and function compared with minimal care. The RESOLVE trial randomly allocated 276 people with CLBP to a new complex treatment strategy, pain education integrated with graded sensorimotor precision training (RESOLVE), or a sham control. The RESOLVE treatment was developed within a theoretical framework to target possible treatment mechanisms associated with CLBP development and persistence. Objective This protocol describes the planned evaluation of these proposed treatment mechanisms. Improved understanding of the mechanisms underpinning the RESOLVE treatment may guide its refinement and implementation. Methods We will use causal mediation analysis to evaluate the proposed treatment mechanisms, including pain self-efficacy, back beliefs, pain catastrophizing, kinesiophobia, back perception, tactile acuity, and movement coordination. The primary outcomes are pain intensity and function at 18 weeks following allocation. Data were collected blind to allocation and hypotheses at baseline (mediators, outcomes, confounders), end of treatment (mediators), and at 18 weeks following allocation (outcomes). We will test the robustness of our findings by conducting planned sensitivity analyses. Results Ethical approval was granted by the University of New South Wales Human Research Ethics Committee (HC15357). A total of 276 participants have been recruited from primary care practices and the community in Sydney, Australia. Conclusions The RESOLVE treatment constitutes a new paradigm for CLBP management with potentially wide-reaching implications. This mechanistic evaluation will provide evidence for the hypothesized treatment mechanisms and help explain why the treatment strategy did or did not have an effect on patient-reported outcomes. These results will help guide the treatment refinement and implementation. Trial Registration Australian and New Zealand Clinical Trials Registry ACTRN12615000610538; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368619&isReview=true International Registered Report Identifier (IRRID) DERR1-10.2196/26053

BackgroundThere is limited evidence for the comparative effectiveness of analgesic medicines for adults with low back pain. This systematic review and network meta-analysis aims to determine the analgesic effect, safety, acceptability, effect on function, and relative rank according to analgesic effect, safety, acceptability, and effect on function of a single course of [an] analgesic medicine(s) or combination of these medicines for people with low back pain.MethodsWe will include published and unpublished randomised trials written in any language that compare an analgesic medicine to either another medicine, placebo/sham, or no intervention in adults with low back pain, grouped according to pain duration: acute (fewer than 6 weeks), sub-acute (6 to 12 weeks), and chronic (greater than 12 weeks). The co-primary outcomes are pain intensity following treatment and safety (adverse events). The secondary outcomes are function and acceptability (all-cause dropouts). We will perform a network meta-analysis to compare and rank analgesic medicines. We will form judgements of confidence in the results using the Confidence in Network Meta-Analysis (CINeMA) methodology.DiscussionThis network meta-analysis will establish which medicine, or combination of medicines, is most effective for reducing pain and safest for adults with low back pain.Systematic review registrationPROSPERO CRD42019145257

Objective To review and assess the methodological quality of randomised controlled trials that test physical therapy interventions for low back pain. Study Design and Setting Systematic review of trials of physical therapy interventions to prevent or treat low back pain (of any duration or type) in participants of any age indexed on the Physiotherapy Evidence Database (PEDro). Existing PEDro scale ratings were used to evaluate methodology quality. Results This review identified 2215 trials. The majority of trials were for adults (n=2136, 96.4%), low back pain without specific aetiology (n=1863, 84.1%), and chronic duration (n=947, 42.8%). The quality of trials improved over time, however most were at risk of bias. Less than half of the trials concealed allocation to intervention (n=813, 36.7%), used intention-to-treat principles (n=778, 35.1%), blinded assessors (n=810, 36.6%), participants (n=174, 7.9%) and therapists (n=39, 1.8%). These findings did not vary by type of therapy. Conclusion The majority of trials that test physical therapy interventions for low back pain have methodological limitations that could bias treatment effect estimates. Greater attention to simple methodological features, such as allocation concealment and the reporting of intention-to-treat effects, would improve the quality of trials testing physical therapy interventions for low back pain.

Background Statistical analysis plans describe the planned data management and analysis for clinical trials. This supports transparent reporting and interpretation of clinical trial results. This paper reports the statistical analysis plan for the RESOLVE clinical trial. The RESOLVE trial assigned participants with chronic low back pain to graded sensory-motor precision training or sham-control. Results We report the planned data management and analysis for the primary and secondary outcomes. The primary outcome is pain intensity at 18-weeks post randomization. We will use mixed-effects models to analyze the primary and secondary outcomes by intention-to-treat. We will report adverse effects in full. We also describe analyses if there is non-adherence to the interventions, data management procedures, and our planned reporting of results. Conclusion This statistical analysis plan will minimize the potential for bias in the analysis and reporting of results from the RESOLVE trial. Trial registration ACTRN12615000610538 ( https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368619 ).

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:To answer the clinical question: ‘what analgesic medicine shall I prescribe this patient with chronic low back pain to reduce their pain?’.The objectives are to determine the analgesic effects, safety, effect on function, and relative rank according to analgesic effect, safety and effect on function of a single course of opioid analgesics, NSAIDs or paracetamol or combinations of these medicines. Refereed/Peer-reviewed

Recently, the degree to which scientific publications provides a reliable source of information has come under intense scrutiny. Reports suggest that a substantial amount of published literature is likely to be biased, distorted, and non-reproducible. This cuts across basic, pre-clinical, and clinical research. It has been estimated that non-reproducible preclinical research consumes $28 billion/year (USD) and that 85% of biomedical research resources are wasted on biased research. The response from the scientific and policy community has been to identify common practices that contribute to the problem, and develop methods to counteract them. This matter is very relevant to the pain field. Understanding the causes of non-reproducible and non-replicable research and its ultimate impact on how we prevent and treat pain should assist pain researchers to improve the reproducibility and replicability of their work. The distinction between reproducibility and replicability is presented in Figure 1 and defined elsewhere. This paper aims to: (1) define drivers of non-reproducible and non-replicable research with examples from pain sciences and broader research fields; and (2) provide an overview of potential solutions and practices that could improve reproducibility and replicability of pain research.

The recent network meta-analysis by Owen and colleagues1 included 89 trials of exercise for chronic low back pain (LBP) and reported low quality evidence that Pilates, stabilisation, resistance and aerobic exercises are the most effective treatments for these patients. We were surprised by how few trials were included and even more surprised by how large the estimates of treatment effect were. For example, with Pilates the effect is reported to be 1.86 standardised mean difference (SMD) in the abstract and 2.32 SMD in online supplementary table 5. These estimates are about 3–4 times effect sizes normally reported for exercise interventions in LBP and so we took a closer look at the review to try to understand what had happened. That investigation revealed some important issues that we would like to share with readers. First, the review has missed a lot of relevant trials. The Cochrane review of exercise for chronic LBP that is currently underway has identified over 350 trials, whereas the Owen review included only 89. Even applying the restrictive selection criteria of the Owen …

As a service to its readership, BJSM publishes educational editorials in order to provide methodological guidance and direction to clinicians and researchers.1 For example, a recent BJSM invited commentary outlined important methodological aspects of randomised controlled trials ( RCTs ) in order to help readers better understand and interpret findings.2 Similarly, a recent BJSM editorial written for clinicians has outlined five essential methodological considerations or ‘hacks’ to consider when reading a systematic review (SR), while another editorial has outlined common pitfalls for authors conducting a SR.3 4 In light of recent suggestions of untrustworthiness of systematic review and meta-analyses (SRMA) findings,5–7 researchers are encouraged to maximise the transparency of their work. Similarly, clinicians and policymakers are encouraged to scrutinise SRMA in order to decide if the findings should influence clinical decisions or policies. The purpose of our two-part educational editorial series is to highlight important methodological aspects of SRMA of the effects of interventions and thus help clinicians make judicious choices when considering whether to accept the findings. By using a worked example, we hope this resource serves as a guide for clinicians when critically appraising SRMA findings and deciding whether (or not) to accept the reported findings or the interpretation of the authors. A SR attempts to collate all empirical evidence that fits prespecified eligibility criteria in order to answer a specific research question.8 An interventional SR specifically assesses the benefits and harms of an intervention and should provide an unbiased, robust, transparent and reproducible overview of the effect of an intervention and the quality of the evidence from identified clinical studies.9 Should the SR contain sufficient and appropriate quantitative data from the included studies, a meta-analysis (MA) can be conducted to provide a pooled estimate of effect, and to examine variation among individual study …

Systematic review and meta-analyses (SRMA) represent the highest quality of evidence of the effects of interventions and have the capacity to usefully inform clinical decisions, reduce research waste and direct policy making.1–4 Interventional SRMA often amalgamate the results of multiple randomised controlled trials (RCTs) to determine the magnitude of the estimate of the effect for a chosen intervention and to examine variation among study outcomes (heterogeneity).5 As such they represent the highest level of evidence to inform clinicians on the usefulness of a given treatment. Of course, the robustness of SRMA findings is dependent on the quality of the trials that have been pooled. The aim of this two-part Educational Editorial Series is to outline a process of scrutiny and analysis for SRMA to facilitate answering the important question ‘Should this SRMA change my practice?’. An understanding of key features of SRMA which have been outlined in related BJSM Educational Editorials is needed by clinicians in order to make this decision.2 6–10 Here, we present a worked example for clinicians illustrating some important considerations when reading an interventional SRMA. Specifically, we highlight the need to consider the pooling of comparators, clinical diversity, comparisons to active control, risk of bias and confidence in the results when interpreting interventional SRMA findings. The example SRMA investigated the efficacy of platelet-rich plasma (PRP) injections for tendinopathy.11 Based on data extracted from 16 RCTs (see online supplementary file 1 for a list of references), the authors reported a moderate treatment effect in favour of PRP with a standard mean difference (SMD) of 0.47 (95% CI 0.22 to 0.72, p

The sacroiliac joint (SIJ) is often considered to be involved when people present for care with low back pain where SIJ is located. However, determining why the pain has arisen can be challenging, especially in the absence of a specific cause such as pregnancy, disease, or trauma, when the SIJ might be identified as a source of symptoms with the help of manual clinical tests. Nonspecific SIJ-related pain is commonly suggested to be causally associated with movement problems in the SIJ(s)—a diagnosis traditionally derived from manual assessment of movements of the SIJ complex. Management choices often consist of patient education, manual treatment, and exercise. Although some elements of management are consistent with guidelines, this Perspective article argues that the assumptions on which these diagnoses and treatments are based are problematic, particularly if they reinforce unhelpful, pathoanatomical beliefs. This article reviews the evidence regarding the clinical detection and diagnosis of SIJ movement dysfunction. In particular, it questions the continued use of assessing movement dysfunction despite mounting evidence undermining the biological plausibility and subsequent treatment paradigms based on such diagnoses. Clinicians are encouraged to align their assessment methods and explanatory models with contemporary science to reduce the risk of their diagnoses and choice of intervention negatively affecting clinical outcomes.

Objective: Systematic reviews of analgesics for low back pain generally include published data only. Obtaining data from unpublished trials is potentially important because they may impact effect sizes in meta-analyses. We determined whether including unpublished data from trial registries changes the effect sizes in meta-analyses of analgesics for low back pain. Study Design and Setting: Trial registries were searched for unpublished data that conformed to the inclusion criteria of n = 5 individual source systematic reviews. We reproduced the meta-analyses using data available from the original reviews and then reran the same analyses with the addition of new unpublished data. Results: Sixteen completed, unpublished, trials were eligible for inclusion in four of the source reviews. Data were available for five trials. We updated the analyses for two of the source reviews. The addition of data from two trials reduced the effect size of muscle relaxants, compared with sham, for recent-onset low back pain from −21.71 (95% CI: −28.23 to −15.19) to −2.34 (95% CI: −3.34 to −1.34) on a 0–100 scale for pain intensity. The addition of data from three trials (one enriched design) reduced the effect size of opioid analgesics, compared with sham, for chronic low back pain from −10.10 (95% CI: −12.81 to −7.39) to −9.31 (95% CI: −11.51 to −7.11). The effect reduced in the subgroup of enriched design studies, from −12.40 (95% CI: −16.90 to −7.91) to −11.34 (95% CI: −15.36 to −7.32), and in the subgroup of nonenriched design studies, from −7.27 (95% CI: −9.97 to −4.57) to −7.19 (95% CI: −9.24 to −5.14). Conclusion: Systematic reviews should include reports of unpublished trials. The result for muscle relaxants conflicts with the conclusion of the published review and recent international guidelines. Adding unpublished data strengthens the evidence that opioid analgesics have small effects on persistent low back pain and more clearly suggests these effects may not be clinically meaningful. Refereed/Peer-reviewed

Background Exercise is recommended for the management of chronic low back pain (CLBP). Trialists have proposed numerous mechanisms to explain why exercise improves pain and function in people with CLBP, but these are yet to be synthesised. Objective To synthesise the proposed mechanisms of benefit for exercise in people with CLBP. Design Review. Methods The Physiotherapy Evidence Database (PEDro) was searched from inception to July 2019. Randomised controlled trials of adults with CLBP, indexed in PEDro as ‘fitness training’, were included. Two reviewers independently screened and extracted data from each study. Data were analysed quantitatively and qualitatively using thematic analysis. Results 186 studies were identified and 110 were included in the analysis. Thirty-six studies (33%) did not provide a mechanism of benefit for exercise in people with CLBP. Of the remaining studies, most provided more than one mechanism, from which 33 unique mechanisms were identified. These were grouped into five themes which, from most to least common, were: neuromuscular (n = 105 (44%)); psychosocial (n = 87 (36%)); neurophysiological (n = 22 (9%)); cardiometabolic (n = 15 (6%)); and tissue healing (n = 12 (5%)). The effects of these proposed mechanisms on outcomes for people with CLBP were seldom examined. Conclusions This review identified a variety of mechanisms proposed in clinical trials to explain why ‘fitness training’ works for people with CLBP, but these mechanisms were seldom tested. Randomised controlled trials investigating the mediating effects of these mechanisms may be warranted to better understand why exercise works for CLBP.

Low back pain (LBP) has a significant impact on the sufferer and society as a whole. Therefore, we read with great interest the Specific Treatment of Problems of the Spine (STOPS) trial1 suggesting that an individualised physiotherapy approach had a favourable outcome when compared with advice in a cohort of participants with LBP lasting for more than 6 weeks. These findings highlight important issues in the design and subsequent interpretation of randomised controlled trials (RCTs) in this area. The primary purpose of RCTs is to determine if an intervention meaningfully improves clinical outcomes. This is realised by comparing the intervention with an appropriate control.2 To determine efficacy, the ideal control is a credible placebo, but this is often difficult to design for non-pharmacological treatments. Thus, an alternative intervention is frequently used as the control. This design does not estimate efficacy; rather, it compares whether one approach is superior to another. Therefore, it is possible for an intervention to be deemed effective when compared with a control for which outcomes are suboptimal. This is relevant in LBP clinical trials and in other …

Persistent low back pain (LBP) is the leading cause of disability globally, for which ever-larger increases in healthcare expenditure have not made a difference in terms of prevalence or burden.1 It is unquestionable that current healthcare is failing individuals with chronic LBP, and we contend that recent evidence from the interventional pain medicine field points clearly to what these failings are. There has been remarkable growth in the use of interventional pain medicine procedures to manage chronic LBP, particularly radiofrequency denervation.2 In this approach, various diagnostic practices are used to identify a peripheral ‘nociceptive driver’, with the presumption that denervation of the peripheral structure will eradicate or significantly reduce pain and improve function.3 The growth in the use of radiofrequency denervation is surprising given that, until recently, the evidence base was equivocal2 and based on conflicting results from a limited number of small trials. A welcome addition to the field was recently provided by Juch et al ,2 who reported on the outcome of three large clinical trials of neuroablative procedures in chronic LBP. All three trials compared guideline-based physical rehabilitation to rehabilitation with the addition of radiofrequency denervation. Despite employing a …