Effectiveness and cost-effectiveness of an individualised, progressive walking and education intervention for the prevention of low back pain recurrence in Australia (WalkBack): a randomised controlled trial.

BACKGROUND: Recurrence of low back pain is common and a substantial contributor to the disease and economic burden of low back pain. Exercise is recommended to prevent recurrence, but the effectiveness and cost-effectiveness of an accessible and low-cost intervention, such as walking, is yet to be established. We aimed to investigate the clinical effectiveness and cost-effectiveness of an individualised, progressive walking and education intervention to prevent the recurrence of low back pain. METHODS: WalkBack was a two-armed, randomised controlled trial, which recruited adults (aged 18 years or older) from across Australia who had recently recovered from an episode of non-specific low back pain that was not attributed to a specific diagnosis, and which lasted for at least 24 h. Participants were randomly assigned to an individualised, progressive walking and education intervention facilitated by six sessions with a physiotherapist across 6 months or to a no treatment control group (1:1). The randomisation schedule comprised randomly permuted blocks of 4, 6, and 8 and was stratified by history of more than two previous episodes of low back pain and referral method. Physiotherapists and participants were not masked to allocation. Participants were followed for a minimum of 12 months and a maximum of 36 months, depending on the date of enrolment. The primary outcome was days to the first recurrence of an activity-limiting episode of low back pain, collected in the intention-to-treat population via monthly self-report. Cost-effectiveness was evaluated from the societal perspective and expressed as incremental cost per quality-adjusted life-year (QALY) gained. The trial was prospectively registered (ACTRN12619001134112). FINDINGS: Between Sept 23, 2019, and June 10, 2022, 3206 potential participants were screened for eligibility, 2505 (78%) were excluded, and 701 were randomly assigned (351 to the intervention group and 350 to the no treatment control group). Most participants were female (565 [81%] of 701) and the mean age of participants was 54 years (SD 12). The intervention was effective in preventing an episode of activity-limiting low back pain (hazard ratio 0·72 [95% CI 0·60-0·85], p=0·0002). The median days to a recurrence was 208 days (95% CI 149-295) in the intervention group and 112 days (89-140) in the control group. The incremental cost per QALY gained was AU$7802, giving a 94% probability that the intervention was cost-effective at a willingness-to-pay threshold of $28 000. Although the total number of participants experiencing at least one adverse event over 12 months was similar between the intervention and control groups (183 [52%] of 351 and 190 [54%] of 350, respectively, p=0·60), there was a greater number of adverse events related to the lower extremities in the intervention group than in the control group (100 in the intervention group and 54 in the control group). INTERPRETATION: An individualised, progressive walking and education intervention significantly reduced low back pain recurrence. This accessible, scalable, and safe intervention could affect how low back pain is managed. FUNDING: National Health and Medical Research Council, Australia.

Single cell RNA sequencing reveals emergent notochord-derived cell subpopulations in the postnatal nucleus pulposus.

Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell-based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus (NP) hold significant promise, but key challenges remain. One of these is the inability of therapeutic cells to effectively mimic the performance of native NP cells, which are unique amongst skeletal cell types in that they arise from the embryonic notochord. In this study, we use single cell RNA sequencing to demonstrate emergent heterogeneity amongst notochord-derived NP cells in the postnatal mouse disc. Specifically, we established the existence of progenitor and mature NP cells, corresponding to notochordal and chondrocyte-like cells, respectively. Mature NP cells exhibited significantly higher expression levels of extracellular matrix (ECM) genes including aggrecan, and collagens II and VI, along with elevated transforming growth factor-beta and phosphoinositide 3 kinase-protein kinase B signaling. Additionally, we identified Cd9 as a novel surface marker of mature NP cells, and demonstrated that these cells were localized to the NP periphery, increased in numbers with increasing postnatal age, and co-localized with emerging glycosaminoglycan-rich matrix. Finally, we used a goat model to show that Cd9+ NP cell numbers decrease with moderate severity disc degeneration, suggesting that these cells are associated with maintenance of the healthy NP ECM. Improved understanding of the developmental mechanisms underlying regulation of ECM deposition in the postnatal NP may inform improved regenerative strategies for disc degeneration and associated low back pain.

The enhanced connectivity between the frontoparietal, somatomotor network and thalamus as the most significant network changes of chronic low back pain.

The prolonged duration of chronic low back pain (cLBP) inevitably leads to changes in the cognitive, attentional, sensory and emotional processing brain regions. Currently, it remains unclear how these alterations are manifested in the interplay between brain functional and structural networks. This study aimed to predict the Oswestry Disability Index (ODI) in cLBP patients using multimodal brain magnetic resonance imaging (MRI) data and identified the most significant features within the multimodal networks to aid in distinguishing patients from healthy controls (HCs). We constructed dynamic functional connectivity (dFC) and structural connectivity (SC) networks for all participants (n = 112) and employed the Connectome-based Predictive Modeling (CPM) approach to predict ODI scores, utilizing various feature selection thresholds to identify the most significant network change features in dFC and SC outcomes. Subsequently, we utilized these significant features for optimal classifier selection and the integration of multimodal features. The results revealed enhanced connectivity among the frontoparietal network (FPN), somatomotor network (SMN) and thalamus in cLBP patients compared to HCs. The thalamus transmits pain-related sensations and emotions to the cortical areas through the dorsolateral prefrontal cortex (dlPFC) and primary somatosensory cortex (SI), leading to alterations in whole-brain network functionality and structure. Regarding the model selection for the classifier, we found that Support Vector Machine (SVM) best fit these significant network features. The combined model based on dFC and SC features significantly improved classification performance between cLBP patients and HCs (AUC=0.9772). Finally, the results from an external validation set support our hypotheses and provide insights into the potential applicability of the model in real-world scenarios. Our discovery of enhanced connectivity between the thalamus and both the dlPFC (FPN) and SI (SMN) provides a valuable supplement to prior research on cLBP.

Cognitive functional therapy with or without movement sensor biofeedback versus usual care for chronic, disabling low back pain (RESTORE): a randomised, controlled, three-arm, parallel group, phase 3, clinical trial.

BACKGROUND: Low back pain is the leading cause of years lived with disability globally, but most interventions have only short-lasting, small to moderate effects. Cognitive functional therapy (CFT) is an individualised approach that targets unhelpful pain-related cognitions, emotions, and behaviours that contribute to pain and disability. Movement sensor biofeedback might enhance treatment effects. We aimed to compare the effectiveness and economic efficiency of CFT, delivered with or without movement sensor biofeedback, with usual care for patients with chronic, disabling low back pain. METHODS: RESTORE was a randomised, controlled, three-arm, parallel group, phase 3 trial, done in 20 primary care physiotherapy clinics in Australia. We recruited adults (aged ≥18 years) with low back pain lasting more than 3 months with at least moderate pain-related physical activity limitation. Exclusion criteria were serious spinal pathology (eg, fracture, infection, or cancer), any medical condition that prevented being physically active, being pregnant or having given birth within the previous 3 months, inadequate English literacy for the study's questionnaires and instructions, a skin allergy to hypoallergenic tape adhesives, surgery scheduled within 3 months, or an unwillingness to travel to trial sites. Participants were randomly assigned (1:1:1) via a centralised adaptive schedule to usual care, CFT only, or CFT plus biofeedback. The primary clinical outcome was activity limitation at 13 weeks, self-reported by participants using the 24-point Roland Morris Disability Questionnaire. The primary economic outcome was quality-adjusted life-years (QALYs). Participants in both interventions received up to seven treatment sessions over 12 weeks plus a booster session at 26 weeks. Physiotherapists and patients were not masked. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12618001396213. FINDINGS: Between Oct 23, 2018 and Aug 3, 2020, we assessed 1011 patients for eligibility. After excluding 519 (51·3%) ineligible patients, we randomly assigned 492 (48·7%) participants; 164 (33%) to CFT only, 163 (33%) to CFT plus biofeedback, and 165 (34%) to usual care. Both interventions were more effective than usual care (CFT only mean difference -4·6 [95% CI -5·9 to -3·4] and CFT plus biofeedback mean difference -4·6 [-5·8 to -3·3]) for activity limitation at 13 weeks (primary endpoint). Effect sizes were similar at 52 weeks. Both interventions were also more effective than usual care for QALYs, and much less costly in terms of societal costs (direct and indirect costs and productivity losses; -AU$5276 [-10 529 to -24) and -8211 (-12 923 to -3500). INTERPRETATION: CFT can produce large and sustained improvements for people with chronic disabling low back pain at considerably lower societal cost than that of usual care. FUNDING: Australian National Health and Medical Research Council and Curtin University.

Opioid analgesia for acute low back pain and neck pain (the OPAL trial): a randomised placebo-controlled trial.

BACKGROUND: Opioid analgesics are commonly used for acute low back pain and neck pain, but supporting efficacy data are scarce. We aimed to investigate the efficacy and safety of a judicious short course of an opioid analgesic for acute low back pain and neck pain. METHODS: OPAL was a triple-blinded, placebo-controlled randomised trial that recruited adults (aged ≥18 years) presenting to one of 157 primary care or emergency department sites in Sydney, NSW, Australia, with 12 weeks or less of low back or neck pain (or both) of at least moderate pain severity. Participants were randomly assigned (1:1) using statistician-generated randomly permuted blocks to guideline-recommended care plus an opioid (oxycodone-naloxone, up to 20 mg oxycodone per day orally) or guideline-recommended care and an identical placebo, for up to 6 weeks. The primary outcome was pain severity at 6 weeks measured with the pain severity subscale of the Brief Pain Inventory (10-point scale), analysed in all eligible participants who provided at least one post-randomisation pain score, by use of a repeated measures linear mixed model. Safety was analysed in all randomly assigned eligible participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000775516). FINDINGS: Between Feb 29, 2016, and March 10, 2022, 347 participants were recruited (174 to the opioid group and 173 to the placebo group). 170 (49%) of 346 participants were female and 176 (51%) were male. 33 (19%) of 174 participants in the opioid group and 25 (15%) of 172 in the placebo group had discontinued from the trial by week 6, due to loss to follow-up and participant withdrawals. 151 participants in the opioid group and 159 in the placebo group were included in the primary analysis. Mean pain score at 6 weeks was 2·78 (SE 0·20) in the opioid group versus 2·25 (0·19) in the placebo group (adjusted mean difference 0·53, 95% CI -0·00 to 1·07, p=0·051). 61 (35%) of 174 participants in the opioid group reported at least one adverse event versus 51 (30%) of 172 in the placebo group (p=0·30), but more people in the opioid group reported opioid-related adverse events (eg, 13 [7·5%] of 174 participants in the opioid group reported constipation vs six [3·5%] of 173 in the placebo group). INTERPRETATION: Opioids should not be recommended for acute non-specific low back pain or neck pain given that we found no significant difference in pain severity compared with placebo. This finding calls for a change in the frequent use of opioids for these conditions. FUNDING: National Health and Medical Research Council, University of Sydney Faculty of Medicine and Health, and SafeWork SA.

Case 328.

HISTORY: A 45-year-old female patient with diffuse osteoarticular pain, particularly low back pain, was referred by a rheumatologist for an updated radiologic evaluation. The patient had experienced these symptoms for many years and was diagnosed with human leukocyte antigen B27-negative spondyloarthritis approximately 11 years prior, based on findings of bilateral erosive sacroiliitis at pelvic radiography (Fig 1A) and bone scintigraphy with technetium 99m methylene diphosphonate (Fig 1B). After 3 years of treatment with a tumor necrosis factor-α inhibitor (adalimumab), which was effective for pain, the patient was lost to follow-up. At the current presentation, approximately 8 years after being lost to follow-up, the patient presented with worsening low back pain. The presence of nonobstructing kidney stones on US images confounded the underlying cause of worsening pain. The patient also experienced fatigue and depressed mood. Routine blood tests revealed a normal blood cell count, creatinine level of 0.64 mg/dL (56.58 µmol/L) (normal range, 0.30-1.1 mg/dL [26.52-97.24 mmol/L]), C-reactive protein level of 1.1 mg/dL (normal, <1 mg/dL), and vitamin D level of 21 ng/mL (52.42 nmol/L) (normal range, 30-100 ng/mL [74.88-249.60 nmol/L]). Noncontrast MRI of the thoracic and lumbar spine (Fig 2), MRI of the sacroiliac joints (Fig 3), and CT of the abdomen and pelvis (Fig 4) were performed.

The impact of contextual effects in exercise therapy for low back pain: a systematic review and meta-analysis.

BACKGROUND: Low back pain is the leading cause of global disability for which exercise therapy is a widely recommended treatment. Research indicates that contextual factors may also influence treatment outcomes in low back pain. Examples include the patient-therapist relationship and other treatment-related circumstances that affect patient expectations. By focusing on the specific treatment effect, clinical trials often ignore the effect of contextual factors, thereby contributing to the so-called efficacy paradox. This means that treatment effects observed in clinical practice are often greater than those reported in clinical trials. This systematic review aims to investigate the proportion of improvement in pain and disability that can be attributed to contextual effects in the outcome of exercise therapy for patients with low back pain. METHODS: A meta-analysis was conducted. PubMed, Embase, and the Cochrane database were searched for eligible articles reporting randomized controlled trials that compared exercise therapy to placebo interventions. Risk of bias was assessed with the Revised Cochrane Risk of Bias Tool. Outcomes of interest were pain and disability. Meta-analysis was carried out to calculate the proportion attributable to contextual effects for both pain and disability. The body of evidence was assessed using the GRADE methodology. RESULTS: Eight studies met the inclusion criteria and were included in the meta-analysis. Five studies were rated as having a moderate risk of bias and two studies had a low risk of bias. Proportion attributable to contextual effects was 0.60 (95% CI 0.40-0.89) for pain and 0.69 (95% CI 0.48-1.00) for disability. Certainty of the evidence as assessed with the GRADE methodology was low. CONCLUSIONS: A large extent of pain and disability improvement after exercise therapy in low back pain is attributable to contextual effects although this conclusion is based on low certainty evidence.

The effects of telehealth-delivered mindfulness meditation, cognitive therapy, and behavioral activation for chronic low back pain: a randomized clinical trial.

BACKGROUND: Chronic low back pain (CLBP) is a significant problem affecting millions of people worldwide. Three widely implemented psychological techniques used for CLBP management are cognitive therapy (CT), mindfulness meditation (MM), and behavioral activation (BA). This study aimed to evaluate the relative immediate (pre- to post-treatment) and longer term (pre-treatment to 3- and 6-month follow-ups) effects of group, videoconference-delivered CT, BA, and MM for CLBP. METHODS: This is a secondary analysis of a three-arm, randomized clinical trial comparing the effects of three active treatments-CT, BA, and MM-with no inert control condition. Participants were N = 302 adults with CLBP, who were randomized to condition. The primary outcome was pain interference, and other secondary outcomes were also examined. The primary study end-point was post-treatment. Intent-to-treat analyses were undertaken for each time point, with the means of the changes in outcomes compared among the three groups using an analysis of variance (ANOVA). Effect sizes and confidence intervals are also reported. RESULTS: Medium-to-large effect size reductions in pain interference were found within BA, CT, and MM (ds from - .71 to - 1.00), with gains maintained at both follow-up time points. Effect sizes were generally small to medium for secondary outcomes for all three conditions (ds from - .20 to - .71). No significant between-group differences in means or changes in outcomes were found at any time point, except for change in sleep disturbance from pre- to post-treatment, improving more in BA than MM (d = - .49). CONCLUSIONS: The findings from this trial, one of the largest telehealth trials of psychological treatments to date, critically determined that group, videoconference-delivered CT, BA, and MM are effective for CLBP and can be implemented in clinical practice to improve treatment access. The pattern of results demonstrated similar improvements across treatments and outcome domains, with effect sizes consistent with those observed in prior research testing in-person delivered and multi-modal psychological pain treatments. Thus, internet treatment delivery represents a tool to scale up access to evidence-based chronic pain treatments and to overcome widespread disparities in healthcare. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03687762.

First trans-diagnostic experiences with a novel micro-choice based concentrated group rehabilitation for patients with low back pain, long COVID, and type 2 diabetes: a pilot study.

BACKGROUND: The health care is likely to break down unless we are able to increase the level of functioning for the growing number of patients with complex, chronic illnesses. Hence, novel high-capacity and cost-effective treatments with trans-diagnostic effects are warranted. In accordance with the protocol paper, we aimed to examine the acceptability, satisfaction, and effectiveness of an interdisciplinary micro-choice based concentrated group rehabilitation for patients with chronic low back pain, long COVID, and type 2 diabetes. METHODS: Patients with low back pain > 4 months sick-leave, long COVID, or type 2 diabetes were included in this clinical trial with pre-post design and 3-month follow-up. The treatment consisted of three phases: (1) preparing for change, (2) the concentrated intervention for 3-4 days, and (3) integrating change into everyday life. Patients were taught and practiced how to monitor and target seemingly insignificant everyday micro-choices, in order to break the patterns where symptoms or habits contributed to decreased levels of functioning or increased health problems. The treatment was delivered to groups (max 10 people) with similar illnesses. Client Satisfaction Questionnaire (CSQ-8)) (1 week), Work and Social Adjustment Scale (WSAS), Brief Illness Perception Questionnaire (BIPQ), and self-rated health status (EQ-5D-5L) were registered at baseline and 3-month follow-up. RESULTS: Of the 241 included participants (57% women, mean age 48 years, range 19-84), 99% completed the concentrated treatment. Treatment satisfaction was high with a 28.9 (3.2) mean CSQ-8-score. WSAS improved significantly from baseline to follow-up across diagnoses 20.59 (0.56) to 15.76 (0.56). BIPQ improved from: 22.30 (0.43) to 14.88 (0.47) and EQ-5D-5L: 0.715 (0.01) to 0.779 (0.01)), all P<0.001. CONCLUSIONS: Across disorders, the novel approach was associated with high acceptability and clinically important improvements in functional levels, illness perception, and health status. As the concentrated micro-choice based treatment format might have the potential to change the way we deliver rehabilitation across diagnoses, we suggest to proceed with a controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05234281.

Obesity and overweight as risk factors for low back pain in children and adolescents: a meta-analysis.

BACKGROUND: Childhood obesity and overweight are associated with musculoskeletal pain, but the association between low back pain (LBP) and overweight/obesity in this population needs clarification. The objective of this meta-analysis is to ascertain the relationship between LBP and obesity/overweight in children and adolescents. METHODS: Various databases and specialized journals were queried from inception to October 2022. Encompassed were all studies examining the association between overweight or obesity and LBP among participants aged 6 to 18 years. The ROBINS-E tool was employed to assess bias. Random-effects models were used to pool results across studies, with location-scale models used to search for moderator variables where evidence of heterogeneity was found. RESULTS: In total, 34 studies were incorporated. Four studies had a low risk of bias, while the remaining studies had some concerns. Nine studies evinced an association between overweight and LBP, in contrast to normal weight, yielding an OR of 1.13 (95% CI 1.10-1.16) and no heterogeneity. Eight studies demonstrated a similar association between obesity and LBP compared to normal weight, with an OR of 1.27 (95% CI 1.20-1.34) and no heterogeneity. Ten studies established an association between overweight/obesity and LBP compared to normal weight, yielding an OR of 1.18 (95% CI 1.14-1.23) and no heterogeneity. Finally, nineteen studies showcased an association between body mass index (BMI) and LBP, with an OR of 1.19 (95% CI 1.03-1.39) with evidence of heterogeneity. For this last analysis, we compared the mean BMI in groups and transformed results to log OR, and then retransformed to OR. CONCLUSION: Overweight and obesity may be risk factors for LBP in children and adolescents. The association between LBP and obesity appears to be stronger than with overweight. However, the analysis revealed considerable heterogeneity and risk of bias across studies.

Allogenic bone marrow-derived mesenchymal stromal cell-based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study).

OBJECTIVES: To assess the efficacy of a single intradiscal injection of allogeneic bone marrow mesenchymal stromal cells (BM-MSCs) versus a sham placebo in patients with chronic low back pain (LBP). METHODS: Participants were randomised in a prospective, double-blind, controlled study to receive either sham injection or intradiscal injection of 20 million allogeneic BM-MSC, between April 2018 and December 2022. The first co-primary endpoint was the rate of responders defined by improvement of the Visual Analogue Scale (VAS) for pain of at least 20% and 20 mm, or improvement of the Oswestry Disability Index (ODI) of 20% between baseline and month 12. The secondary structural co-primary endpoint was assessed by the disc fluid content measured by quantitative MRI T2, between baseline and month 12. Secondary endpoints included pain VAS, ODI, the Short Form (SF)-36 and the minimal clinically important difference in all timepoints (1, 3, 6, 12 and 24 months). We determined the immune response associated with allogeneic cell injection between baseline and 6 months. Serious adverse events (SAEs) were recorded. RESULTS: 114 patients were randomised (n=58, BM-MSC group; n=56, sham placebo group). At 12 months, the primary outcome was not reached (74% in the BM-MSC group vs 69% in the placebo group; p=0.77). The groups did not differ in all secondary outcomes. No SAE related to the intervention occurred. CONCLUSIONS: While our study did not conclusively demonstrate the efficacy of allogeneic BM-MSCs for LBP, the procedure was safe. Long-term outcomes of MSC therapy for LBP are still being studied. TRIAL REGISTRATION NUMBER: EudraCT 2017-002092-25/ClinicalTrials.gov: NCT03737461.

Three-dimensional freehand ultrasonography to measure muscle volume of the lumbar multifidus: Reliability of processing technique and validity through comparison to magnetic resonance imaging.

There is a growing interest in muscle characteristics of the lumbar multifidus related to low back pain, but findings between studies are inconsistent. One of the issues explaining these conflicting findings might be the use of two-dimensional measures of cross-sectional area and thickness of the lumbar multifidus in most studies, which might be a suboptimal representation of the entire muscle volume. A three-dimensional volumetric assessment, combined with standardized imaging and processing measurement protocols, is highly recommended to quantify spinal muscle morphology. Three-dimensional freehand ultrasonography is a technique with large potential for daily clinical practice. It is achieved by combining conventional two-dimensional ultrasound with a motion-tracking system, recording the position and orientation of the ultrasound transducer during acquisition, resulting in a three-dimensional reconstruction. This study investigates intra- and interprocessor reliability for the quantification of muscle volume of the lumbar multifidus based on three-dimensional freehand ultrasound and its validity, in 31 patients with low back pain and 20 healthy subjects. Two processors manually segmented the lumbar multifidus on three-dimensional freehand ultrasound images using Stradwin software following a well-defined method. We assessed the concurrent validity of the measurement of multifidus muscle volume using three-dimensional freehand ultrasound compared with magnetic resonance imaging in 10 patients with low back pain. Processing reliability and agreement were determined using intraclass correlation coefficients, Bland-Altman plots, and calculation of the standard error of measurement and minimal detectable change, while validity was defined based on correlation analysis. The processing of three-dimensional freehand ultrasound images to measure lumbar multifidus volume was reliable. Good to excellent intraclass correlation coefficients were found for intraprocessor reliability. For interprocessor reliability, the intraclass correlation coefficients were moderate to good, emphasizing the importance of processing guidelines and training. A single processor analysis is preferred in clinical studies or when small differences in muscle volume are expected. The correlation between magnetic resonance imaging and three-dimensional freehand ultrasound measurements of lumbar multifidus volume was moderate to good but with a systematically smaller multifidus volume measured on three-dimensional freehand ultrasound. These results provide opportunities for both researchers and clinicians to reliably assess muscle structure using three-dimensional freehand ultrasound in patients with low back pain and to monitor changes related to pathology or interventions. To allow implementation in both research and clinical settings, guidelines on three-dimensional freehand ultrasound processing and training were provided.

Effects of Chronic Pain Diagnoses on the Antidepressant Efficacy of Transcranial Magnetic Stimulation.

OBJECTIVE: Major depressive disorder (MDD) and chronic pain are highly comorbid and bidirectionally related. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex is effective in treating MDD, but additional research is needed to determine if chronic pain interferes with rTMS for MDD. METHODS: Participants were 124 veterans ( Mage = 49.14, SD = 13.83) scheduled for 30 sessions of rTMS across 6 weeks. Depression severity was monitored weekly using the Patient Health Questionnaire-9 (PHQ-9). Having any pain diagnosis, low back pain, or headache/migraine were assessed by chart review. We fit latent basis models to estimate total change by pain diagnosis in depression scores and quadratic latent growth models to examine differences in growth rates. Then, we computed χ2 tests of group differences in response (PHQ-9 reduction ≥50%) and remission rates (final PHQ-9 < 5). RESULTS: A total of 92 participants (74%) had a documented pain diagnosis, 58 (47%) had low back pain, and 32 (26%) had headache/migraine. In growth models, depression scores initially decreased (linear slope estimate = -2.04, SE = 0.26, p < .0001), but the rate of decrease slowed over time (quadratic slope estimate = 0.18, SE = 0.04, p < .001). Overall change was not different as a function of any pain diagnosis ( p = .42), low back pain (p = .11 ), or headache/migraine ( p = .28). However, we found that low back pain was a negative predictor of response ( p = .032). CONCLUSIONS: These data support rTMS as a viable treatment option for comorbid populations. Although patients with comorbid chronic pain conditions are likely to receive benefit from rTMS for depression, adjunctive pain treatment may be indicated.

Trends in Chiropractic Care and Physical Rehabilitation Use Among Adults with Low Back Pain in the United States, 2002 to 2018.

BACKGROUND: While nonpharmacologic treatments are increasingly endorsed as first-line therapy for low back pain (LBP) in clinical practice guidelines, it is unclear if use of these treatments is increasing or equitable. OBJECTIVE: Examine national trends in chiropractic care and physical rehabilitation (occupational/physical therapy (OT/PT)) use among adults with LBP. DESIGN/SETTING: Serial cross-sectional analysis of the National Health Interview Survey, 2002 to 2018. PARTICIPANTS: 146,087 adults reporting LBP in prior 3 months. METHODS: We evaluated the association of survey year with chiropractic care or OT/PT use in prior 12 months. Logistic regression with multilevel linear splines was used to determine if chiropractic care or OT/PT use increased after the introduction of clinical guidelines. We also examined trends in use by age, sex, race, and ethnicity. When trends were similar over time, we present differences by these demographic characteristics as unadjusted ORs using data from all respondents. RESULTS: Between 2002 and 2018, less than one-third of adults with LBP reported use of either chiropractic care or OT/PT. Rates did not change until 2016 when uptake increased with the introduction of clinical guidelines (2016-2018 vs 2002-2015, OR = 1.15; 95% CI: 1.10-1.19). Trends did not differ significantly by sex, race, or ethnicity (p for interactions > 0.05). Racial and ethnic disparities in chiropractic care or OT/PT use were identified and persisted over time. For example, compared to non-Hispanic adults, either chiropractic care or OT/PT use was lower among Hispanic adults (combined OR = 0.62, 95% CI: 0.65-0.73). By contrast, compared to White adults, Black adults had similar OT/PT use (OR = 0.98; 95% CI: 0.94-1.03) but lower for chiropractic care use (OR = 0.50; 95% CI: 0.47-0.53). CONCLUSIONS: Although use of chiropractic care or OT/PT for LBP increased after the introduction of clinical guidelines in 2016, only about a third of US adults with LBP reported using these services between 2016 and 2018 and disparities in use have not improved.

Association of Opioid Use Disorder Diagnosis with Management of Acute Low Back Pain: A Medicare Retrospective Cohort Analysis.

BACKGROUND: Practice guidelines recommend nonpharmacologic and nonopioid therapies as first-line pain treatment for acute pain. However, little is known about their utilization generally and among individuals with opioid use disorder (OUD) for whom opioid and other pharmacologic therapies carry greater risk of harm. OBJECTIVE: To determine the association between a pre-existing OUD diagnosis and treatment of acute low back pain (aLBP). DESIGN: Retrospective cohort study using 2016-2019 Medicare data. PARTICIPANTS: Fee-for-service Medicare beneficiaries with a new episode of aLBP. MAIN MEASURES: The main independent variable was OUD diagnosis measured prior to the first LBP claim (i.e., index date). Using multivariable logistic regressions, we assessed the following outcomes measured within 30 days of the index date: (1) nonpharmacologic therapies (physical therapy and/or chiropractic care), and (2) prescription opioids. Among opioid recipients, we further assessed opioid dose and co-prescription of gabapentin. Analyses were conducted overall and stratified by receipt of physical therapy, chiropractic care, opioid fills, or gabapentin fills during the 6 months before the index date. KEY RESULTS: We identified 1,263,188 beneficiaries with aLBP, of whom 3.0% had OUD. Two-thirds (65.8%) did not receive pain treatments of interest at baseline. Overall, nonpharmacologic therapy receipt was less prevalent and opioid and nonopioid pharmacologic therapies were more common among beneficiaries with OUD than those without OUD. Beneficiaries with OUD had lower odds of receiving nonpharmacologic therapies (aOR = 0.62, 99%CI = 0.58-0.65) and higher odds of prescription opioid receipt (aOR = 2.24, 99%CI = 2.17-2.32). OUD also was significantly associated with increased odds of opioid doses ≥ 90 morphine milligram equivalents/day (aOR = 2.43, 99%CI = 2.30-2.56) and co-prescription of gabapentin (aOR = 1.15, 99%CI = 1.09-1.22). Similar associations were observed in stratified groups though magnitudes differed. CONCLUSIONS: Medicare beneficiaries with aLBP and OUD underutilized nonpharmacologic pain therapies and commonly received opioids at high doses and with gabapentin. Complementing the promulgation of practice guidelines with implementation science could improve the uptake of evidence-based nonpharmacologic therapies for aLBP.

Paget Disease of Bone Harboring Bone Metastatic Neuroendocrine Cancer: A Case Report.

In this case report, we describe an uncommon case of neuroendocrine cancer of unknown origin began with cauda equina syndrome in a patient affected by Paget disease of bone (PDB). A 76-year-old man with diagnosis of PDB, without history of pain or bone deformity, developed sudden severe low back pain. Bone alkaline phosphatase was increased and MRI and whole-body scintigraphy confirmed the localization of the disease at the third vertebra of the lumbar spine. Treatment with Neridronic Acid was started, but after only 2 weeks of therapy anuria and bowel occlusion occurred together with lower limb weakness and walking impairment. Cauda equina syndrome consequent to spinal stenosis at the level of L2-L3 was diagnosed after admission to Emergency Department and the patient underwent neurosurgery for spinal medulla decompression. The histologic results showed a complete subversion of bone structure in neoplastic tissue, consistent with metastatic neuroendocrine carcinoma of unknown origin. In conclusion, low back pain in the elderly may require deep investigation to individuate rare diseases. In asymptomatic patients with apparently stable PDB, the sudden appearance of pain or neurologic symptoms may alert the clinician for the possibility of other superimposing diseases, like bone metastases.

Evolving role of VIADISC for chronic low back and discogenic pain: a narrative review.

INTRODUCTION: Chronic lower back pain is a leading cause of disability and healthcare spending worldwide. Discogenic pain, pain originating from the intervertebral disk, is a common etiology of chronic lower back pain. Currently, accepted treatments for chronic discogenic pain focus only on the management of symptoms, such as pain. There are no approved treatments that stop or reverse degenerating intervertebral discs. Biologic therapies promoting disc regeneration have been developed to expand treatment options. VIADISC™ NP, is a viable disc allograft supplementation that, in a recent trial, demonstrated a significant reduction in pain and increased function in patients suffering from symptomatic degenerative disc disease. AREAS COVERED: This manuscript summarizes the epidemiology and etiology of low back pain, the pathophysiology of degenerative disc disease, current treatments, and a need for newer therapies. The rationale behind intradiscal biologics for the treatment of symptomatic degenerative disc disease is also discussed. EXPERT OPINION: Characterization of the biology leading to disc degeneration has allowed for the development of intradiscal biologics. They may soon be capable of preventing and reversing disc degeneration. Clinical trials have shown promise, but further research into efficacy and safety is needed before these therapies are widely employed.

Gait assessment in a female rat Sprague Dawley model of disc-associated low back pain.

PURPOSE: Gait disturbances are common in human low back pain (LBP) patients, suggesting potential applicability to rodent LBP models. This study aims to assess the influence of disc-associated LBP on gait in female Sprague Dawley rats and explore the utility of the open-source Gait Analysis Instrumentation and Technology Optimized for Rodents (GAITOR) suite as a potential alternative tool for spontaneous pain assessment in a previously established LBP model. MATERIALS AND METHODS: Disc degeneration was surgically induced using a one-level disc scrape injury method, and microcomputed tomography was used to assess disc volume loss. After disc injury, axial hypersensitivity was evaluated using the grip strength assay, and an open field test was used to detect spontaneous pain-like behavior. RESULTS: Results demonstrated that injured animals exhibit a significant loss in disc volume and reduced grip strength. Open field test did not detect significant differences in distance traveled between sham and injured animals. Concurrently, animals with injured discs did not display significant gait abnormalities in stance time imbalance, temporal symmetry, spatial symmetry, step width, stride length, and duty factor compared to sham. However, comparisons with reference values of normal gait reported in prior literature reveal that injured animals exhibit mild deviations in forelimb and hindlimb stance time imbalance, forelimb temporal symmetry, and hindlimb spatial symmetry at some time points. CONCLUSIONS: This study concludes that the disc injury may have very mild effects on gait in female rats within 9 weeks post-injury and recommends future in depth dynamic gait analysis and longer studies beyond 9 weeks to potentially detect gait.

Integrating randomized and observational studies to estimate optimal dynamic treatment regimes.

Sequential multiple assignment randomized trials (SMARTs) are the gold standard for estimating optimal dynamic treatment regimes (DTRs), but are costly and require a large sample size. We introduce the multi-stage augmented Q-learning estimator (MAQE) to improve efficiency of estimation of optimal DTRs by augmenting SMART data with observational data. Our motivating example comes from the Back Pain Consortium, where one of the overarching aims is to learn how to tailor treatments for chronic low back pain to individual patient phenotypes, knowledge which is lacking clinically. The Consortium-wide collaborative SMART and observational studies within the Consortium collect data on the same participant phenotypes, treatments, and outcomes at multiple time points, which can easily be integrated. Previously published single-stage augmentation methods for integration of trial and observational study (OS) data were adapted to estimate optimal DTRs from SMARTs using Q-learning. Simulation studies show the MAQE, which integrates phenotype, treatment, and outcome information from multiple studies over multiple time points, more accurately estimates the optimal DTR, and has a higher average value than a comparable Q-learning estimator without augmentation. We demonstrate this improvement is robust to a wide range of trial and OS sample sizes, addition of noise variables, and effect sizes.

A trial-based economic evaluation of the CaFaSpA referral strategy for axial spondyloarthritis.

OBJECTIVE: To assess the cost-utility from healthcare and societal perspectives of the digital CaFaSpA referral strategy (CS) for axial spondyloarthritis (axSpA) in primary care patients with chronic low back pain (CLBP). METHOD: A cluster randomized controlled trial was performed in the Netherlands. General practice units were randomized into CS or usual care (UC). Economic evaluation was performed from the healthcare and societal perspectives within a 12-month time horizon. Outcome measures encompassed disability [Roland-Morris Disability Questionnaire (RMDQ)] and health-related quality of life (EQ-5D-3L). Direct medical (iMTA Medical Consumption Questionnaire) and indirect costs (iMTA Productivity Cost Questionnaire), including productivity loss, were evaluated. Incremental cost-utility ratios (ICURs) were calculated. RESULTS: The study included 90 GP clusters with 563 patients (CS: n = 260; UC: n = 303) (mean ± sd age 36.3 ± 7.5 years; 66% female). After 12 months, no minimal important differences in outcomes were observed for RMDQ (-0.21, 95%CI -1.52 to 1.13) or EQ-5D (-0.02, 95%CI -0.08 to 0.05). However, total costs were significantly lower in the CS group owing to lower productivity loss costs. The ICUR for RMDQ was €18,059 per point decrease and €220,457 per quality-adjusted life year increase. CONCLUSIONS: Digital referral did not decrease the overall healthcare status of patients after 1 year of follow-up and appears to be more cost-effective than UC. Therefore, CS can be used as an appropriate primary care referral model for CLBP patients at risk for axSpA. This will accelerate timely provision of care by the right caregiver.