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.

Adherence to low back pain clinical guidelines in Australian hospital emergency departments: A public and private comparison.

Managing LBP via clinical practice guidelines in healthcare settings is recommended, yet burgeoning evidence suggests adherence is suboptimal in emergency department settings. Whether adherence differs between public and private settings is unknown. A retrospective audit of two Australian emergency departments matched 86 private patients to 86 public patients by age ( ± 5 years), sex (male/female) and LBP duration (first time/history of LBP). Patient charts were reviewed according to the Australian clinical guidelines for the management of LBP. Guidelines were considered individually and via a collective guideline adherence score (GAS). Management GAS was lower in private patients compared to public patients (d [95 %CI]: -0.67 [-0.98, -0.36], P < 0.001). Public patients were more likely to have documentation of guideline-based advice (OR [95 %CI]: 4.4 [2.4, 8.4], P < 0.001) and less likely to be sent for imaging (OR [95 %CI]: 5.0 [2.6, 9.4], P < 0.001). Private patients were more likely to have documented screening for psychosocial risk factors (OR [95 %CI]: 21.8 [9.1, 52.1], P < 0.001) and more likely to receive guideline-based medication prescriptions at patient discharge (OR [95 %CI]: 2.2 [1.2, 4.2], P = 0.013). Differences exist in public and private hospital emergency department guideline adherence. Exploring barriers and facilitators underpinning these differences will assist in guiding future implementation science approaches.

Boosting treatment outcomes via the patient-practitioner relationship, treatment-beliefs or therapeutic setting. A systematic review with meta-analysis of contextual effects in chronic musculoskeletal pain.

OBJECTIVE: To ascertain whether manipulating contextual effects (e.g. interaction with patients, or beliefs about treatments) boosted the outcomes of non-pharmacological and non-surgicaltreatments for chronic primary musculoskeletal pain. DESIGN: Systematic review of randomized controlled trials. DATA SOURCES: We searched for trials in six databases, citation tracking, and clinical trials registers. We included trials that compared treatments with enhanced contextual effects with the same treatments without enhancement in adults with chronic primary musculoskeletal pain. DATA SYNTHESIS: The outcomes of interest were pain intensity, physical functioning, global ratings of improvement, quality of life, depression, anxiety, and sleep. We evaluated risk of bias and certainty of the evidence using Cochrane Risk of Bias tool 2.0 and the GRADE approach, respectively. RESULTS: Of 17637 records, we included 10 trials with 990 participants and identified 5 ongoing trials. The treatments were acupuncture, education, exercise training, and physical therapy. The contextual effects that were improved in the enhanced treatments were patient-practitioner relationship, patient beliefs and characteristics, therapeutic setting/environment, and treatment characteristics. Our analysis showed that improving contextual effects in non-pharmacological and non-surgical treatments may not make much difference on pain intensity (mean difference [MD] : -1.77, 95%-CI: [-8.71; 5.16], k = 7 trials, N = 719 participants, Scale: 0-100, GRADE: Low)) or physical functioning (MD: -0.27, 95%-CI: [-1.02; 0.49], 95%-PI: [-2.04; 1.51], k = 6 , N = 567, Scale: 0-10, GRADE: Low) in the short-term and at later follow-ups. Sensitivity analyses revealed similar findings. CONCLUSION: Whilst evidence gaps exist, per current evidence it may not be possible to achieve meaningful benefit for patients with chronic musculoskeletal pain by manipulating the context of non-pharmacological and non-surgical treatments. TRIAL REGISTRATION: This systematic review was prospectively registered in PROSPERO (registration number: CRD42023391601).

Contextual effects: how to, and how not to, quantify them.

The importance of contextual effects and their roles in clinical care controversial. A Cochrane review published in 2010 concluded that placebo interventions lack important clinical effects overall, but that placebo interventions can influence patient-reported outcomes such as pain and nausea. However, systematic reviews published after 2010 estimated greater contextual effects than the Cochrane review, which stems from the inappropriate methods employed to quantify contextual effects. The effects of medical interventions (i.e., the total treatment effect) can be divided into three components: specific, contextual, and non-specific. We propose that the most effective method for quantifying the magnitude of contextual effects is to calculate the difference in outcome measures between a group treated with placebo and a non-treated control group. Here, we show that other methods, such as solely using the placebo control arm or calculation of a 'proportional contextual effect,' are limited and should not be applied. The aim of this study is to provide clear guidance on best practices for estimating contextual effects in clinical research.

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.

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 Impact of Exercise Prescription Variables on Intervention Outcomes in Musculoskeletal Pain: An Umbrella Review of Systematic Reviews.

BACKGROUND: Musculoskeletal pain conditions are the largest contributors to disability and healthcare burden globally. Exercise interventions improve physical function and quality of life in individuals with musculoskeletal pain, yet optimal exercise prescription variables (e.g. duration, frequency, intensity) are unclear. OBJECTIVE: We aimed to examine evidence gaps, methodological quality and exercise prescription recommendations in systematic reviews of exercise for musculoskeletal pain. METHODS: In our prospectively registered umbrella review, PubMed, SPORTDiscus, Cochrane Database of Systematic Reviews, EMBASE, and CINAHL were searched from inception to 14 February 2023. Backward citation tracking was performed. We included peer-reviewed, English language, systematic reviews and meta-analyses of randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared exercise with conservative treatment, placebo or other exercise interventions in adults with musculoskeletal pain. Data were extracted from the following groups of reviews based on their reporting of exercise prescription data and analysis of the relationship between prescription variables and outcomes: (1) those that did not report any exercise prescription data, (2) those that reported exercise prescription data but did not perform a quantitative analysis and (3) those that performed a quantitative analysis of the relationship between exercise prescription variables and outcomes. Outcome measures were physical function, pain, mental health, adverse effects and adherence to treatment. AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews) was used to assess methodological quality. RESULTS: From 6757 records, 274 systematic reviews were included. 6.6% of reviews did not report any exercise prescription data, and only 10.9% quantitatively analyzed the relationship between prescription variables and the outcome(s). The overall methodological quality was critically low in 85% of reviews. CONCLUSION: High methodological quality evidence is lacking for optimal exercise training prescription variables in individuals with musculoskeletal pain. To better inform practice and evidence gaps, future systematic reviews should (1) identify optimum exercise prescription variables, for example, via dose-response (network) meta-analysis, (2) perform high-quality reviews per AMSTAR-2 criteria and (3) include outcomes of mental health, adverse events and exercise adherence. PROSPERO REGISTRATION NUMBER: CRD42021287440 ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021287440 ).

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.

Telemedicine for Patients with Musculoskeletal Pain Lacks High-Quality Evidence on Delivery Modes and Effectiveness: An Umbrella Review.

Background: Musculoskeletal (MSK) pain is the leading cause of disability worldwide. Telemedicine is of growing importance, yet impacts on treatment efficacy remain unclear. Objective: This umbrella review (CRD42022298047) examined the effectiveness of telemedicine interventions on pain intensity, disability, psychological function, quality of life, self-efficacy, and adverse events in MSK pain. Methods: PubMed, SPORTDiscus, Cochrane Library, EMBASE, and CINAHL were searched from inception to August 9, 2022, for systematic reviews with meta-analysis, including telemedicine-delivered exercise, education, and psychological interventions, in randomized controlled trials (RCTs). AMSTAR-2 was implemented. Standardized mean differences (SMDs; negative favors telemedicine) were extracted as effect estimates. Results: Of 1,135 records, 20 reviews (RCTs: n = 97, participants: n = 15,872) were included. Pain intensity SMDs were -0.66 to 0.10 for mixed pain (estimates: n = 16), -0.64 to -0.01 for low-back pain (n = 9), -0.31 to -0.15 for osteoarthritis (n = 7), -0.29 for knee pain (n = 1), -0.66 to -0.58 for fibromyalgia (n = 2), -0.16 for back pain (n = 1), and -0.09 for rheumatic disorders (n = 1). Disability SMDs were -0.50 to 0.10 for mixed pain (n = 14), -0.39 to 0.00 for low-back pain (n = 8), -0.41 to -0.04 for osteoarthritis (n = 7), -0.22 for knee pain (n = 1), and -0.56 for fibromyalgia (n = 1). Methodological quality was "critically low" for 17 reviews. Effectiveness tended to favor telemedicine for all secondary outcomes. Conclusions: Primary RCTs are required that compare telemedicine interventions with in-person delivery of the intervention (noninferiority trials), consider safety, assess videoconferencing, and combine different treatment approaches.

Effectiveness of Exercise Interventions for Preventing Neck Pain: A Systematic Review With Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To update the evidence on the effectiveness of exercise interventions to prevent episodes of neck pain. DESIGN: Systematic review with meta-analysis. LITERATURE SEARCH: MEDLINE, Embase, CENTRAL, CINAHL, SPORTDiscus, PEDro, and trial registries from inception to December 2, 2022. Forward and backward citation searches. STUDY SELECTION CRITERIA: Randomized controlled trials (RCTs) that enrolled adults without neck pain at baseline and compared exercise interventions to no intervention, placebo/sham, attention control, or minimal intervention. Military populations and astronauts were excluded. DATA SYNTHESIS: Random-effects meta-analysis. Risk of bias was assessed using the Cochrane RoB 2 tool. The certainty of evidence was judged according to the GRADE approach. RESULTS: Of 4703 records screened, 5 trials (1722 participants at baseline) were included and eligible for meta-analysis. Most (80%) participants were office workers. Risk of bias was rated as some concerns for 2 trials and high for 3 trials. There was moderate-certainty evidence that exercise interventions probably reduce the risk of a new episode of neck pain (OR, 0.49; 95% confidence interval: 0.31, 0.76) compared to no or minimal intervention in the short-term (≤12 months). The results were not robust to sensitivity analyses for missing outcome data. CONCLUSION: There was moderate-certainty evidence supporting exercise interventions for reducing the risk for an episode of neck pain in the next 12 months. The clinical significance of the effect is unclear. J Orthop Sports Phys Ther 2023;53(10):1-16. Epub: 8 September 2023. doi:10.2519/jospt.2023.12063.

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.

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.

Does adding exercise or physical activity to pharmacological osteoporosis therapy in patients with increased fracture risk improve bone mineral density and lower fracture risk? A systematic review and meta-analysis.

This prospectively registered systematic review and meta-analysis examines whether exercise (EX) training has an additive effect to osteoanabolic and/or antiresorptive pharmacological therapy (PT) in people with osteoporosis on bone mineral density (BMD), bone turnover markers (BTMs), fracture healing, and fractures. Four databases (inception to 6 May 2022), 5 trial registries, and reference lists were searched. Included were randomized controlled trials comparing the effect of EX + PT vs. PT with regard to BMD, BTM, fracture healing, and fractures. Risk of bias was assessed using the Cochrane RoB2 and certainty of evidence by the GRADE approach. Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman adjustment was used to estimate standardized mean differences and 95% confidence intervals. Out of 2593 records, five RCTs with 530 participants were included. Meta-analysis showed with very low certainty evidence and wide confidence intervals that EX + PT compared to PT had larger effect sizes for BMD at 12 months at the hip (SMD [95%CI]: 0.18 [- 1.71; 2.06], n = 3 studies), tibia (0.25 [- 4.85; 5.34], n = 2), lumbar spine (0.20 [- 1.15; 1.55], n = 4), and forearm (0.05 [- 0.35; 0.46], n = 3), but not femoral neck (- 0.03 [- 1.80; 1.75], n = 3). Furthermore, no improvement was revealed for BTM such as bone ALP (- 0.68 [- 5.88; 4.53], n = 3), PINP (- 0.74 [- 10.42; 8.93], n = 2), and CTX-I (- 0.69 [- 9.61; 8.23], n = 2), but with very wide confidence intervals. Three potentially relevant ongoing trials were identified via registries. No data were found for fracture healing or fracture outcomes. It remains unclear whether EX has an additive impact to PT in people with osteoporosis. High-quality, adequately powered, targetted RCTs are required. PROTOCOL REGISTRATION: PROSPERO CRD42022336132.

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.

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.