Feasibility and safety of combining repetitive transcranial magnetic stimulation and quadriceps strengthening exercise for chronic pain in knee osteoarthritis: A study protocol for a pilot randomised controlled trial

Introduction Knee osteoarthritis is a leading cause of disability, resulting in pain and reduced quality of life. Exercise is the cornerstone of conservative management but effects are, at best, moderate. Early evidence suggests that repetitive transcranial magnetic stimulation (rTMS) applied over the primary motor cortex (M1) may improve the effect of exercise in knee osteoarthritis. This pilot study aims to (1) determine the feasibility, safety and participant-rated response to an intervention adding M1 rTMS to exercise in knee osteoarthritis; (2) elucidate physiological mechanisms in response to the intervention; (3) provide data to conduct a sample size calculation for a fully powered trial. Methods and analysis This is a pilot randomised, assessor-blind, therapist-blind and participant-blind, sham-controlled trial. Thirty individuals with painful knee osteoarthritis will be recruited and randomly allocated to receive either: (1) active rTMS+exercise or (2) sham rTMS+exercise intervention. Participants will receive 15 min of either active or sham rTMS immediately prior to 30 min of supervised muscle strengthening exercise (2×/week, 6 weeks) and complete unsupervised home exercises. Outcome measures of feasibility, safety, pain, function and physiological mechanisms will be assessed before and/or after the intervention. Feasibility and safety will be analysed using descriptive analysis. Within-group and between-group comparisons of pain and function will be conducted to examine trends of efficacy. Ethics and dissemination This study has been approved by the University of New South Wales Human Research Ethics Committee (HC210954). All participants will provide written informed consent. The study results will be submitted for peer-reviewed publication. Trial registration number ACTRN12621001712897p

Human lower leg muscles grow asynchronously

Muscle volume must increase substantially during childhood growth to generate the power required to propel the growing body. One unresolved but fundamental question about childhood muscle growth is whether muscles grow at equal rates; that is, if muscles grow in synchrony with each other. In this study, we used magnetic resonance imaging (MRI) and advances in artificial intelligence methods (deep learning) for medical image segmentation to investigate whether human lower leg muscles grow in synchrony. Muscle volumes were measured in 10 lower leg muscles in 208 typically developing children (eight infants aged less than 3 months and 200 children aged 5 to 15 years). We tested the hypothesis that human lower leg muscles grow synchronously by investigating whether the volume of individual lower leg muscles, expressed as a proportion of total lower leg muscle volume, remains constant with age. There were substantial age-related changes in the relative volume of most muscles in both boys and girls (p < 0.001). This was most evident between birth and five years of age but was still evident after five years. The medial gastrocnemius and soleus muscles, the largest muscles in infancy, grew faster than other muscles in the first five years. The findings demonstrate that muscles in the human lower leg grow asynchronously. This finding may assist early detection of atypical growth and allow targeted muscle-specific interventions to improve the quality of life, particularly for children with neuromotor conditions such as cerebral palsy.</p

Development of a booster intervention for graded sensorimotor retraining (RESOLVE) in people with persistent low back pain: A nested, randomised, feasibility trial

Introduction: Low back pain contributes to an increasing global health burden exacerbated by unsustained improvements from current treatments. There is a need to develop, and test interventions to maintain initial improvements from low back pain treatments. One option is to implement a booster intervention. This study aimed to develop and test the feasibility of implementing a booster intervention delivered remotely to supplement the benefits from a complex intervention for chronic low back pain. Method: This study was nested in the RESOLVE trial. The booster intervention was developed by an expert group, including a clinical psychologist, exercise physiologist and physiotherapists, and based on a motivational interviewing framework. We developed a conversational flow chart to support the clinician to guide participants towards achieving their pre-specified personal goals and future low back pain self-management. Participants with chronic low back pain who were aged over 18 years and fluent in English were recruited. The booster intervention was delivered in one session, remotely, by telephone. The intervention was considered feasible if: participants were able to be contacted orsession; there were sufficient willing participants (7/10. Results: Fifty participants with chronic non-specific low back pain were recruited to test the feasibility of implementing the booster intervention. Less than three contact attempts were necessary to arrange the booster session, only one participant declined to participate. Participants perceived the session to be beneficial; on a 0 to 10 scale of perceived benefit, the average score recorded was 8.3 (SD 2.0). Clinicians also reported a moderate perceived benefit to the participant; the average score recorded by clinicians was 6.3 (SD 1.6). Conclusion: We developed a step by step, simple booster intervention that was perceived to be beneficial to participants with chronic low back pain. The booster can feasibly be delivered remotely following a complex intervention

Investigating the mechanisms of graded sensorimotor precision training in adults with chronic nonspecific low back pain: Protocol for a causal mediation analysis of the RESOLVE Trial

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): DERR1-10.2196/2605

Non‐pharmacological and non‐surgical treatments for low back pain in adults: An overview of Cochrane Reviews

This is a protocol for a Cochrane Review (overview). The objectives are as follows: 1. Provide accessible, high‐quality evidence on the effects of non‐pharmacological interventions for people with LBP.2. To highlight areas of remaining uncertainty and gaps in the evidence regarding the effects of non‐pharmacological interventions for people with LBP

Effect of graded sensorimotor retraining on pain intensity in patients with crhonic low back pain: a randomized clinical trial

Importance The effects of altered neural processing, defined as altering neural networks responsible for perceptions of pain and function, on chronic pain remains unclear. Objective To estimate the effect of a graded sensorimotor retraining intervention (RESOLVE) on pain intensity in people with chronic low back pain. Design, Setting, and Participants This parallel, 2-group, randomized clinical trial recruited participants with chronic (\u3e3 months) nonspecific low back pain from primary care and community settings. A total of 276 adults were randomized (in a 1:1 ratio) to the intervention or sham procedure and attention control groups delivered by clinicians at a medical research institute in Sydney, Australia. The first participant was randomized on December 10, 2015, and the last was randomized on July 25, 2019. Follow-up was completed on February 3, 2020. Interventions Participants randomized to the intervention group (n = 138) were asked to participate in 12 weekly clinical sessions and home training designed to educate them about and assist them with movement and physical activity while experiencing lower back pain. Participants randomized to the control group (n = 138) were asked to participate in 12 weekly clinical sessions and home training that required similar time as the intervention but did not focus on education, movement, and physical activity. The control group included sham laser and shortwave diathermy applied to the back and sham noninvasive brain stimulation. Main Outcomes and Measures The primary outcome was pain intensity at 18 weeks, measured on an 11-point numerical rating scale (range, 0 [no pain] to 10 [worst pain imaginable]) for which the between-group minimum clinically important difference is 1.0 point. Results Among 276 randomized patients (mean [SD] age, 46 [14.3] years; 138 [50%] women), 261 (95%) completed follow-up at 18 weeks. The mean pain intensity was 5.6 at baseline and 3.1 at 18 weeks in the intervention group and 5.8 at baseline and 4.0 at 18 weeks in the control group, with an estimated between-group mean difference at 18 weeks of −1.0 point ([95% CI, −1.5 to −0.4]; P = .001), favoring the intervention group. Conclusions and Relevance In this randomized clinical trial conducted at a single center among patients with chronic low back pain, graded sensorimotor retraining, compared with a sham procedure and attention control, significantly improved pain intensity at 18 weeks. The improvements in pain intensity were small, and further research is needed to understand the generalizability of the findings. Trial Registration ANZCTR Identifier: ACTRN1261500061053

Reporting of observational studies explicitly aiming to emulate randomized trials: a systematic review

Importance: observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice.Objective: to assess the reporting of observational studies that explicitly aimed to emulate a target trial.Evidence Review: we searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation.Findings: a total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation.Conclusion and Relevance: in this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts