Running is acceptable and efficacious in adults with non-specific chronic low back pain: the ASTEROID randomised controlled trial.

OBJECTIVES: Running is one of the most accessible forms of exercise, yet its suitability for adults with chronic low back pain (LBP) is unknown. This study assessed the efficacy and acceptability of running in adults with chronic LBP. METHODS: This two-arm parallel (1:1) individually randomised controlled trial allocated 40 participants (mean (SD) age: 33 (6) years, female: 50%) with non-specific chronic LBP to a 12-week intervention or waitlist control. The intervention was a progressive run-walk interval programme comprising three 30-min sessions per week that were digitally delivered and remotely supported by an exercise physiologist. Efficacy outcomes were self-reported pain intensity (100-point visual analogue scale) and disability (Oswestry Disability Index). Acceptability outcomes were attrition, adherence and adverse events. RESULTS: At 12-week follow-up, the intervention improved average pain intensity (mean net difference (95% CI): -15.30 (-25.33, -5.27) points, p=0.003), current pain intensity (-19.35 (-32.01, -6.69) points, p=0.003) and disability (-5.20 (-10.12, -0.24) points, P=0.038), compared with control. There was no attrition, and mean (SD) training adherence was 70% (20%; ie, 2.1 of 3 sessions per week). Nine non-serious adverse events deemed likely study-related were reported (lower limb injury/pain: n=7, syncope associated with an underlying condition: n=1, LBP: n=1). CONCLUSIONS: A run-walk programme was considered an acceptable intervention by the participants to improve the pain intensity and disability in individuals aged 18-45 years with non-specific chronic LBP when compared with the control. An individualised and conservative run-walk programme should be considered a suitable form of physical activity for adults with chronic LBP. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry: ACTRN12622001276741. Registered on 29 September 2022.

Do Smokers' Perceptions of the Harmfulness of Nicotine Replacement Therapy and Nicotine Vaping Products as Compared to Cigarettes Influence Their Use as an Aid for Smoking Cessation? Findings from the ITC Four Country Smoking and Vaping Surveys.

INTRODUCTION: This study examined whether smokers' harm perceptions of nicotine replacement therapy (NRT) and nicotine vaping products (NVPs) relative to cigarettes predicted their subsequent use as smoking cessation aids during their last quit attempt (LQA). AIMS AND METHODS: We analyzed data from 1,315 current daily smokers (10+ cigarettes per day) who were recruited at Wave 1 (2016), and who reported making a quit attempt by Wave 2 (2018) of the International Tobacco Control Four Country Smoking and Vaping Surveys in Australia, Canada, England, and the United States. We used multinomial logistic regression models to examine prospective associations between harm perceptions of (a) NRT and (b) NVPs and their use at LQA, controlling for socio-demographic and other potential confounders. RESULTS: Smokers who perceive that (a) NRT and (b) NVPs are much less harmful than cigarettes were more likely to subsequently use the respective product as an aid than using no aid or other aids during LQA (adjusted relative risk ratio [aRRR] = 3.79, 95%CI = 2.16-6.66; and aRRR = 2.11, 95%CI = 1.29-3.45, respectively) compared to smokers who perceive these products as equally or more harmful. Additionally, those who perceive NVPs as much less harmful than cigarettes were less likely to use NRT as a quit aid (aRRR = 0.34, 95%CI = 0.20-0.60). No country variations for these associations were found. CONCLUSIONS: This study found that smokers' perceptions of the harmfulness of (a) NRT and (b) NVPs relative to cigarettes predicted the respective product use when trying to quit smoking. Corrective education targeting misperceptions of nicotine products' relative harmfulness may facilitate their use for smoking cessation. IMPLICATIONS: Nicotine replacement therapy and nicotine vaping products are two commonly used smoking cessation aids. This study demonstrates that misperceptions of the harms of nicotine products relative to cigarettes influence their use for smoking cessation. Believing that nicotine vaping products are much less harmful than cigarette smoking may lead some smokers to prefer these products over nicotine replacement therapy to aid smoking cessation. Education targeting misperceptions of nicotine products' harmfulness relative to cigarettes may enable smokers to make informed choices about which are appropriate to aid smoking cessation.

Interventions for promoting evidence-based guideline-consistent surgery in low back pain: a systematic review and meta-analysis of randomised controlled trials.

PURPOSE: Examine the effectiveness of interventions to approach guideline-adherent surgical referrals for low back pain assessed via systematic review and meta-analysis. METHODS: Five databases (10 September 2021), Google Scholar, reference lists of relevant systematic reviews were searched and forward and backward citation tracking of included studies were implemented. Randomised controlled/clinical trials in adults with low back pain of interventions to optimise surgery rates or referrals to surgery or secondary referral were included. Bias was assessed using the Cochrane ROB2 tool and evidence certainty via Grading of Recommendations Assessment, Development and Evaluation (GRADE). A random effects meta-analysis with a Paule Mandel estimator plus Hartung-Knapp-Sidik-Jonkman method was used to calculate the odds ratio and 95% confidence interval, respectively. RESULTS: Of 886 records, 6 studies were included (N = 258,329) participants; cluster sizes ranged from 4 to 54. Five studies were rated as low risk of bias and one as having some concerns. Two studies reporting spine surgery referral or rates could only be pooled via combination of p values and gave evidence for a reduction (p = 0.021, Fisher's method, risk of bias: low). This did not persist with sensitivity analysis (p = 0.053). For secondary referral, meta-analysis revealed a non-significant odds ratio of 1.07 (95% CI [0.55, 2.06], I2 = 73.0%, n = 4 studies, Grading of Recommendations Assessment, Development and Evaluation [GRADE] evidence certainty: very low). CONCLUSION: Few RCTs exist for interventions to improve guideline-adherent spine surgery rates or referral. Clinician education in isolation may not be effective. Future RCTs should consider organisational and/or policy level interventions. PROSPERO REGISTRATION: CRD42020215137.

Which specific modes of exercise training are most effective for treating low back pain? Network meta-analysis.

OBJECTIVE: Examine the effectiveness of specific modes of exercise training in non-specific chronic low back pain (NSCLBP). DESIGN: Network meta-analysis (NMA). DATA SOURCES: MEDLINE, CINAHL, SPORTDiscus, EMBASE, CENTRAL. ELIGIBILITY CRITERIA: Exercise training randomised controlled/clinical trials in adults with NSCLBP. RESULTS: Among 9543 records, 89 studies (patients=5578) were eligible for qualitative synthesis and 70 (pain), 63 (physical function), 16 (mental health) and 4 (trunk muscle strength) for NMA. The NMA consistency model revealed that the following exercise training modalities had the highest probability (surface under the cumulative ranking (SUCRA)) of being best when compared with true control: Pilates for pain (SUCRA=100%; pooled standardised mean difference (95% CI): -1.86 (-2.54 to -1.19)), resistance (SUCRA=80%; -1.14 (-1.71 to -0.56)) and stabilisation/motor control (SUCRA=80%; -1.13 (-1.53 to -0.74)) for physical function and resistance (SUCRA=80%; -1.26 (-2.10 to -0.41)) and aerobic (SUCRA=80%; -1.18 (-2.20 to -0.15)) for mental health. True control was most likely (SUCRA≤10%) to be the worst treatment for all outcomes, followed by therapist hands-off control for pain (SUCRA=10%; 0.09 (-0.71 to 0.89)) and physical function (SUCRA=20%; -0.31 (-0.94 to 0.32)) and therapist hands-on control for mental health (SUCRA=20%; -0.31 (-1.31 to 0.70)). Stretching and McKenzie exercise effect sizes did not differ to true control for pain or function (p>0.095; SUCRA<40%). NMA was not possible for trunk muscle endurance or analgesic medication. The quality of the synthesised evidence was low according to Grading of Recommendations Assessment, Development and Evaluation criteria. SUMMARY/CONCLUSION: There is low quality evidence that Pilates, stabilisation/motor control, resistance training and aerobic exercise training are the most effective treatments, pending outcome of interest, for adults with NSCLBP. Exercise training may also be more effective than therapist hands-on treatment. Heterogeneity among studies and the fact that there are few studies with low risk of bias are both limitations.

Domains of Chronic Low Back Pain and Assessing Treatment Effectiveness: A Clinical Perspective.

Nonspecific chronic low back pain (CLBP) is a common clinical condition that has impacts at both the individual and societal level. Pain intensity is a primary outcome used in clinical practice to quantify the severity of CLBP and the efficacy of its treatment; however, pain is a subjective experience that is impacted by a multitude of factors. Moreover, differences in effect sizes for pain intensity are not observed between common conservative treatments, such as spinal manipulative therapy, cognitive behavioral therapy, acupuncture, and exercise training. As pain science evolves, the biopsychosocial model is gaining interest in its application for CLBP management. The aim of this article is to discuss our current scientific understanding of pain and present why additional factors should be considered in conservative CLBP management. In addition to pain intensity, we recommend that clinicians should consider assessing the multidimensional nature of CLBP by including physical (disability, muscular strength and endurance, performance in activities of daily living, and body composition), psychological (kinesiophobia, fear-avoidance, pain catastrophizing, pain self-efficacy, depression, anxiety, and sleep quality), social (social functioning and work absenteeism), and health-related quality-of-life measures, depending on what is deemed relevant for each individual. This review also provides practical recommendations to clinicians for the assessment of outcomes beyond pain intensity, including information on how large a change must be for it to be considered "real" in an individual patient. This information can guide treatment selection when working with an individual with CLBP.

How to Interpret Effect Sizes for Biopsychosocial Outcomes and Implications for Current Research.

Biopsychosocial factors are associated with pain, but they can be difficult to compare. One way of comparing them is to use standardized mean differences. Previously, these effects sizes have been termed as small, medium, or large, if they are bigger than or equal to, respectively, .2, .5, or .8. These cut-offs are arbitrary and recent evidence showed that they need to be reconsidered. We argue it is necessary to determine cut-offs for each biopsychosocial factor. To achieve this, we propose 3 potential approaches: 1) examining, for each factor, how the effect size differs depending upon disease severity; 2) using an existing minimum clinically important difference to anchor the large effect size; and 3) define cut-offs by comparing data from people with and without pain. This is important for pain research, as exploring these methodologies has potential to improve comparability of biopsychosocial factors and lead to more directed treatments. We note assumptions and limitations of these methods that should also be considered. PERSPECTIVE: Standardized mean differences can estimate effect sizes between groups and could theoretically allow for comparison of biopsychosocial factors. However, common thresholds to define effect sizes are arbitrary and likely differ based on outcome. We propose methods that could overcome this and be used to derive biopsychosocial outcome-specific effect sizes.

The importance of context (placebo effects) in conservative interventions for musculoskeletal pain: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Contextual effects (e.g. patient expectations) may play a role in treatment effectiveness. This study aimed to estimate the magnitude of contextual effects for conservative, non-pharmacological interventions for musculoskeletal pain conditions. A systematic review and meta-analysis of randomized controlled trials (RCTs) that compared placebo conservative non-pharmacological interventions to no treatment for musculoskeletal pain. The outcomes assessed included pain intensity, physical functioning, health-related quality of life, global rating of change, depression, anxiety and sleep at immediate, short-, medium- and/or long-term follow-up. DATABASES AND DATA TREATMENT: MEDLINE, EMBASE, CINAHL, Web of Science Core Collection, CENTRAL and SPORTDiscus were searched from inception to September 2021. Trial registry searches, backward and forward citation tracking and searches for prior systematic reviews were completed. The Cochrane risk of bias 2 tool was implemented. RESULTS: The study included 64 RCTs (N = 4314) out of 8898 records. For pain intensity, a mean difference of (MD: -5.32, 95% confidence interval (CI): -7.20, -3.44, N = 57 studies with 74 outcomes, GRADE: very low) was estimated for placebo interventions. A small effect in favour of the placebo interventions for physical function was estimated (SMD: -0.22, 95% CI: -0.35, -0.09; N = 37 with 48 outcomes, GRADE: very low). Similar results were found for a broad range of patient-reported outcomes. Meta-regression analyses did not explain heterogeneity among analyses. CONCLUSION: The study found that the contextual effect of non-pharmacological conservative interventions for musculoskeletal conditions is likely to be small. However, given the known effect sizes of recommended evidence-based treatments for musculoskeletal conditions, it may still contribute an important component. SIGNIFICANCE: Contextual effects of non-pharmacological conservative interventions for musculoskeletal conditions are likely to be small for a broad range of patient-reported outcomes (pain intensity, physical function, quality of life, global rating of change and depression). Contextual effects are unlikely, in isolation, to offer much clinical care. But these factors do have relevance in an overall treatment context as they provide almost 30% of the minimally clinically important difference.

Exercise prescription variables predict reductions in pain intensity in adults with chronic low back pain: secondary analysis of a randomised controlled trial.

Objectives: The relationship between exercise training variables and clinical outcomes in low back pain (LBP) is unclear. The current study aimed to explore the relationship between exercise training parameters and pain intensity in individuals with chronic LBP. Methods: This study is a secondary analysis of a previously reported randomised controlled trial comparing the effects of general strength and conditioning to motor control exercises and manual therapy. This secondary analysis includes adults with chronic LBP (n=20) randomised to the general strength and conditioning programme only. Primary outcomes of this analysis were exercise training parameters (time under tension, rating of perceived exertion (RPE), session duration, session-RPE and training frequency) and pain intensity (0-100 mm visual analogue acale) measured every 2 weeks from baseline to 6 months follow-up. Linear mixed models with random effects (participants) and allowance for heterogeneity of variance (study date) were used to determine the association between pain intensity and training parameters over time. Results: Mean (95% CI) pain intensity decreased over time from baseline to 6 months follow-up by 10.7 (2.8 to 18.7) points (p=0.008). Over the 6-month intervention, lower pain intensity was associated with higher RPE (ß (95% CI) -27.168 (-44.265 to -10.071), p=0.002), greater time under tension (-0.029 (-0.056 to -0.001), p=0.040) and shorter session duration (1.938 (0.011 to 3.865), p=0.049). Conclusion: During 6 months of general strength and conditioning, lower pain intensity was associated with higher participant-reported training intensity, greater volume and shorter session duration. To ensure positive outcomes to exercise training, these variables should be monitored on a short-term basis. Trial registration number: ACTRN12615001270505.

DOSage of Exercise for chronic low back pain disorders (DOSE): protocol for a systematic review with dose-response network meta-analysis.

Chronic low back disorders are the leading cause of direct and indirect healthcare burden globally. Exercise training improves pain intensity, mental health and physical function. However, the optimal prescription variables are unknown. We aim to compare the efficacy of various exercise dosages for chronic low back disorders to identify the optimal prescription variables. Six databases (Medline, SPORTDiscus, CINAHL, PsycINFO, EMBASE and CENTRAL), trial registries (ClinicalTrials.gov and WHO International Clinical Trials Registry Platform) and reference lists of prior systematic reviews will be searched, and we will conduct forward and backward citation tracking. We will include peer-reviewed randomised controlled trials (individual, cluster or cross-over trials) published in English or German language comparing exercise training to other exercise training or non-exercise training interventions (conservative, non-surgical, non-pharmacological, non-invasive treatments, placebo, sham, usual/standard care, no-treatment control, waitlist control) in adults with chronic low back disorders. Outcomes will include pain intensity, disability, mental health, adverse events, adherence rate, dropout rate and work capacity. Version 2 of the Cochrane risk-of-bias tool will be employed. The dose will be categorised as cumulative dose (total and weekly minutes of exercise training) and individual dose prescription variables (intervention duration, session duration, frequency and intensity). Dose-response model-based network meta-analysis will be used to assess the comparative efficacy of different exercise doses to determine a dose-response relationship. The certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation. Information about optimal exercise training dosage will help in enhancing treatment outcomes.

The Interaction Between Psychosocial Factors and Exercise-Induced Hypoalgesia in Pain-Free Nurses.

Purpose: This cross-sectional study aimed to investigate whether psychosocial factors were predictive for exercise-induced hypoalgesia (EIH) in pain-free adults. Methods: A sample of 38 pain-free nurses with a mean (SD) age of 26 (6) years were included in this study. Participants completed psychosocial questionnaires prior to physical tests. Pressure pain threshold (PPT) was assessed bilaterally at the calves (local), lower back (semi-local) and forearm (remote) before and immediately after a maximal graded cycling exercise test. Separate linear mixed effects models were used to determine change in PPT before and after cycling exercise (EIH). Multiple linear regression for all psychosocial variables and best subset regression was used to identify predictors of EIH at all locations. Results: The relative mean increase in PPT at the forearm, lumbar, calf, and globally (all sites pooled) was 6.0% (p<0.001), 10.1% (p<0.001), 13.9% (p<0.001), and 10.2% (p=0.013), respectively. Separate best subset multiple linear regression models at the forearm (predictors; Multidimensional Scale of Perceived Social Support (MSPSS) total), lumbar (predictors; MSPSS total, Pain Catastrophizing Scale (PCS) total, Depression Anxiety Stress Scale (DASS) depression), calf (predictors; MSPSS friends, PCS total), and global (predictors; MSPSS friends, PCS total) accounted for 7.5% (p=0.053), 13% (p=0.052), 24% (p=0.003), and 17% (p=0.015) of the variance, respectively. Conclusion: These findings confirm that cycling exercise produced EIH in young nurses and provided preliminary evidence to support the interaction between perceived social support, pain catastrophizing and EIH. Further investigation is required to better understand psychological and social factors that mediate EIH on a larger sample of adults at high risk of developing chronic musculoskeletal pain.

Classifying Nonspecific Low Back Pain for Better Clinical Outcomes: Current Challenges and Paths Forward.

SYNOPSIS: Low back pain classification systems are structured assessments used to guide choices of more specific treatments. Classification systems examined in randomized controlled trials have limited effects on pain intensity and disability compared to nonclassified interventions. Potential reasons for the lack of efficacy include (1) failing to assess multidimensional factors that contribute to pain, (2) relying on clinician judgement, (3) low accessibility, and (4) poor classification reliability. Overcoming these limitations is critical to deciding whether classification systems can improve clinical practice. Only once these limitations are addressed, can we feel certain about the efficacy, or lack thereof, of classification systems. This Viewpoint guides the reader through some limitations of common classification approaches and presents a path forward to open-access, reliable, and multidimensional precision medicine for managing low back pain. J Orthop Sports Phys Ther 2023;53(5):1-5. Epub: 5 April 2023. doi:10.2519/jospt.2023.11658.

Towards data-driven biopsychosocial classification of non-specific chronic low back pain: a pilot study.

The classification of non-specific chronic low back pain (CLBP) according to multidimensional data could guide clinical management; yet recent systematic reviews show this has not been attempted. This was a prospective cross-sectional study of participants with CLBP (n = 21) and age-, sex- and height-matched pain-free controls (n = 21). Nervous system, lumbar spinal tissue and psychosocial factors were collected. Dimensionality reduction was followed by fuzzy c-means clustering to determine sub-groups. Machine learning models (Support Vector Machine, k-Nearest Neighbour, Naïve Bayes and Random Forest) were used to determine the accuracy of classification to sub-groups. The primary analysis showed that four factors (cognitive function, depressive symptoms, general self-efficacy and anxiety symptoms) and two clusters (normal versus impaired psychosocial profiles) optimally classified participants. The error rates in classification models ranged from 4.2 to 14.2% when only CLBP patients were considered and increased to 24.2 to 37.5% when pain-free controls were added. This data-driven pilot study classified participants with CLBP into sub-groups, primarily based on psychosocial factors. This contributes to the literature as it was the first study to evaluate data-driven machine learning CLBP classification based on nervous system, lumbar spinal tissue and psychosocial factors. Future studies with larger sample sizes should validate these findings.

Effects of pharmacotherapy on sleep-related outcomes in adults with chronic low back pain: A systematic review and meta-analysis of randomised controlled trials.

Background: Adults with chronic low back pain (CLBP) suffer impaired sleep. Medications for CLBP can impact sleep which in turn may influence treatment outcomes. This systematic review and meta-analysis examined the effects of pharmacotherapy (any type) on sleep in adults with CLBP. Methods: In this systematic review and meta-analysis, we searched PubMed, CINAHL, SPORTDiscus, PsycINFO, EMBASE, and CENTRAL from inception to 10 July 2022. Randomised controlled trials that investigated the effects of pharmacotherapy on sleep in adults with CLBP were included. Manual citation search of relevant systematic reviews and included studies were also conducted. Mean change from baseline for sleep outcomes (e.g., sleep quality, total sleep time, wake after sleep onset) was the effect of interest. Pairwise inverse-variance random effect meta-analysis was performed to impute pooled estimates (Hedges' g or risk ratios). The Hartung-Knapp-Sidik-Jonkman method was used where there were ≤5 studies. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used for evaluating the certainty of evidence. This study was registered with PROSPERO (CRD42022309419). Findings: Assessment of 3959 records resulted in nine studies (n = 2927) being included. Pharmacotherapy for CLBP management had a small, yet unlikely clinically significant, effect on improving sleep in adults with CLBP, when compared to placebo (g [95% CI]: -0.23 [-0.37, -0.09], p = .0009; I 2  = 30.1%; n = 1433; studies: n = 8; GRADE: low). Notably, no eligible studies investigated the effect of sleep medications in this population, despite being within the scope of this review. Interpretation: Pharmacotherapy used to manage CLBP provided improvements in sleep in adults with CLBP. Given that these effects were small and unlikely clinically significant, clinicians could consider alternative treatments (e.g., non-pharmacological interventions) for managing sleep in adults with CLBP. However, low to very low certainty of evidence precluded strong conclusions. To improve certainty of evidence and confidence in the effect estimates, future research needs to use robust method to minimise bias. Additional research evaluating multiple sleep characteristics, using both validated objective and subjective measures, is also warranted to further investigate the influence of distinct sleep parameters. Funding: The Summer Research Scholarship from the Appleton Institute, Central Queensland University, Australia.

Assessing safety and treatment efficacy of running on intervertebral discs (ASTEROID) in adults with chronic low back pain: protocol for a randomised controlled trial.

Poor intervertebral disc (IVD) health is associated with low back pain (LBP). This 12-week parallel randomised controlled trial will evaluate the efficacy of a progressive interval running programme on IVD health and other clinical outcomes in adults with chronic LBP. Participants will be randomised to either a digitally delivered progressive interval running programme or waitlist control. Participants randomised to the running programme will receive three individually tailored 30 min community-based sessions per week over 12 weeks. The waitlist control will undergo no formal intervention. All participants will be assessed at baseline, 6 and 12 weeks. Primary outcomes are IVD health (lumbar IVD T2 via MRI), average LBP intensity over the prior week (100-point visual analogue scale) and disability (Oswestry Disability Index). Secondary outcomes include a range of clinical measures. All outcomes will be analysed using linear mixed models. This study has received ethical approval from the Deakin University Human Research Ethics Committee (ID: 2022-162). All participants will provide informed written consent before participation. Regardless of the results, the findings of this study will be disseminated, and anonymised data will be shared via an online repository. This will be the first study to evaluate whether a progressive interval running programme can improve IVD health in adults with chronic LBP. Identifying conservative options to improve IVD health in this susceptible population group has the potential to markedly reduce the burden of disease. This study was registered via the Australian New Zealand Clinical Trials Registry on 29 September 2022 (ACTRN12622001276741).

Evidence- and data-driven classification of low back pain via artificial intelligence: Protocol of the PREDICT-LBP study.

In patients presenting with low back pain (LBP), once specific causes are excluded (fracture, infection, inflammatory arthritis, cancer, cauda equina and radiculopathy) many clinicians pose a diagnosis of non-specific LBP. Accordingly, current management of non-specific LBP is generic. There is a need for a classification of non-specific LBP that is both data- and evidence-based assessing multi-dimensional pain-related factors in a large sample size. The "PRedictive Evidence Driven Intelligent Classification Tool for Low Back Pain" (PREDICT-LBP) project is a prospective cross-sectional study which will compare 300 women and men with non-specific LBP (aged 18-55 years) with 100 matched referents without a history of LBP. Participants will be recruited from the general public and local medical facilities. Data will be collected on spinal tissue (intervertebral disc composition and morphology, vertebral fat fraction and paraspinal muscle size and composition via magnetic resonance imaging [MRI]), central nervous system adaptation (pain thresholds, temporal summation of pain, brain resting state functional connectivity, structural connectivity and regional volumes via MRI), psychosocial factors (e.g. depression, anxiety) and other musculoskeletal pain symptoms. Dimensionality reduction, cluster validation and fuzzy c-means clustering methods, classification models, and relevant sensitivity analyses, will classify non-specific LBP patients into sub-groups. This project represents a first personalised diagnostic approach to non-specific LBP, with potential for widespread uptake in clinical practice. This project will provide evidence to support clinical trials assessing specific treatments approaches for potential subgroups of patients with non-specific LBP. The classification tool may lead to better patient outcomes and reduction in economic costs.

Chronic back pain sub-grouped via psychosocial, brain and physical factors using machine learning.

Chronic back pain (CBP) is heterogenous and identifying sub-groups could improve clinical decision making. Machine learning can build upon prior sub-grouping approaches by using a data-driven approach to overcome clinician subjectivity, however, only binary classification of pain versus no-pain has been attempted to date. In our cross-sectional study, age- and sex-matched participants with CBP (n = 4156) and pain-free controls (n = 14,927) from the UkBioBank were included. We included variables of body mass index, depression, loneliness/social isolation, grip strength, brain grey matter volumes and functional connectivity. We used fuzzy c-means clustering to derive CBP sub-groups and Support Vector Machine (SVM), Naïve Bayes, k-Nearest Neighbour (kNN) and Random Forest classifiers to determine classification accuracy. We showed that two variables (loneliness/social isolation and depression) and five clusters were optimal for creating sub-groups of CBP individuals. Classification accuracy was greater than 95% for when CBP sub-groups were assessed only, while misclassification in CBP sub-groups increased to 35-53% across classifiers when pain-free controls were added. We showed that individuals with CBP could sub-grouped and accurately classified. Future research should optimise variables by including specific spinal, psychosocial and nervous system measures associated with CBP to create more robust sub-groups that are discernible from pain-free controls.

Relative contributions of the nervous system, spinal tissue and psychosocial health to non-specific low back pain: Multivariate meta-analysis.

BACKGROUND AND OBJECTIVES: Nervous system, psychosocial and spinal tissue biomarkers are associated with non-specific low back pain (nsLBP), though relative contributions are unclear. DATABASES AND DATA TREATMENT: MEDLINE, EMBASE, CINAHL, PsycINFO and SPORTDiscus were searched up to 25 March 2020. Related reviews and reference lists were also screened. Observational studies examining structural and functional nervous system biomarkers (e.g. quantitative sensory tests, structural and functional brain measures), psychosocial factors (e.g. mental health, catastrophizing) and structural spinal imaging biomarkers (e.g. intervertebral disc degeneration, paraspinal muscle size) between nsLBP and pain-free controls were included. For multivariate meta-analysis, two of three domains were required in each study. Random-effects pairwise and multivariate meta-analyses were performed. GRADE approach assessed evidence certainty. Newcastle-Ottawa scale assessed risk of bias. Main outcomes were the effect size difference of domains between nsLBP and pain-free controls. RESULTS: Of 4519 unique records identified, 33 studies (LBP = 1552, referents = 1322) were meta-analysed. Psychosocial state (Hedges' g [95%CI]: 0.90 [0.69-1.10], p < 0.001) in nsLBP showed larger effect sizes than nervous system (0.31 [0.13-0.49], p < 0.001; difference: 0.61 [0.36-0.86], p < 0.001) and spine imaging biomarkers (0.55 [0.37-0.73], p < 0.001; difference: 0.36 [0.04-0.67], p = 0.027). The relationship between domains changes depending on if pain duration is acute or chronic. CONCLUSIONS: Psychosocial effect sizes in nsLBP are greater than those for spinal imaging and nervous system biomarkers. Limitations include cross-sectional design of studies included and inference of causality. Future research should investigate the clinical relevance of these effect size differences in relation to pain intensity and disability. STUDY REGISTRATION: PROSPERO-CRD42020159188. SIGNIFICANCE: Spinal structural lesions (e.g. intervertebral disc degeneration), psychosocial (e.g. depression) and nervous system factors (detected by e.g. quantitative sensory tests, structural and functional measures) contribute to non-specific low back pain. However, psychosocial factors may be more compromised than nervous system and spinal imaging biomarkers. This relationship depends on if the pain is acute or chronic. These findings underscore that the 'non-specific' label in back pain should be reconsidered, and more specific multidimensional categories evaluated to guide patient management.