Background:Individuals with chronic low back pain (LBP) often present with significant physical dysfunction. The underlying cause is difficult to diagnose due to the heterogeneous nature of LBP categories. Methods:Two hundred and fifty-six patients were assessed as having either nociceptive (NC) or nociplastic (NP) chronic low back pain using validated surveys, including the PainDETECT Questionnaire and a chronic overlapping pain condition screener. Additional covariates of anxiety, depression, and fear avoidance were evaluated using standard surveys. Physical function was judged objectively using a sit-to-stand test (STS; quantified using marker-less motion capture calculated kinematic scores and movement metrics) and subjectively (PROMIS-physical function survey). Demographics (age, sex, BMI), psychological factors, and biomechanical outcomes were compared across pain categories using nonparametric statistics and regression modeling. Results:Compared to the NC group, the NP group was significantly older (NP: 61.0 ± 21.0, NC: 53.5 ± 29.3, p = 0.03) and reported higher levels of anxiety (NP: 51.2 ± 17.4, NC: 48.0 ± 13.4, p = 0.002) and depression (NP: 49.0 ± 14.7, NC: 41.0 ± 10.8, p = 0.009). NP also had worse perceived physical function (PROMIS-PF) (NP: 39.3 ± 6.9, NC: 42.1 ± 7.3, p < 0.001) and slower STS times (NP: 12.5 ± 6.1 s, NC: 12.0 ± 5.8, p = 0.03). Despite these differences, the NP group exhibited biomechanical function closer to the healthy control average motion trajectory (K-score; NP: 77.6 ± 8.1, NC: 75.6 ± 8.1, p = 0.03) during the STS task. Regression models evaluating the association between biomechanical variables and pain categories, while adjusting for age, sex, and BMI, identified significant differences between pain categories only for PROMIS-physical function. Conclusion:While individuals with nociplastic pain reported lower perceived physical function and exhibited differences in demographic and psychological factors, pain categories were not significant predictors of objective biomechanical measures after adjusting for age, sex, and BMI. However, pain category was a significant predictor of PROMIS-PF, suggesting that it is more closely associated with perceived functional limitations than with quantitative biomechanical performance.

OBJECTIVE:This study identifies distinct biobehavioral phenotypes among patients with chronic low back pain (cLBP) using Latent Profile Analysis (LPA). METHODS:These phenotypes were derived from baseline data from two cohorts within the NIH HEAL BACPAC consortium: BACKHOME, a large nationwide e-cohort (N = 3025) utilized for model training, and COMEBACK as external test set, a deep phenotyping cohort (N = 450) utilized for generalization. The analysis incorporated variables including pain characteristics, psychosocial factors, lifestyle habits, and social determinants of health. Model fit was optimized via 10-fold cross-validation with 100 bootstraps and evaluated using Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), and Entropy(uncertainty). RESULTS:Four classes were identified: Class 1 ("High Distress and Maladaptive Behaviors") displayed high levels of anxiety, depression, and fear avoidance. Class 2 ("Resilient and Adaptive Coping") exhibited low maladaptive behaviors and high pain self-efficacy. Class 3 ("Intermediate Maladaptive Patterns") represented moderate levels of psychological and behavioral challenges, while Class 4 ("Emotionally Regulated with High Pain Burden") demonstrated strong emotional regulation despite significant pain burden. Class sizes were 701, 413, 893, and 947 for the train set, and 127, 108, 95, and 68 for the test set, respectively. Fit metrics supported the model's performance and generalizability (BACKHOME (train set): AIC = 77 792, BIC = 78 338, Entropy = 0.82; COMEBACK(test set): AIC = 72 437, BIC = 73 880, Entropy = 0.81). Statistical analysis revealed significant differences between classes (P < .05) in key variables such as pain self-efficacy, fear avoidance, and emotional awareness, and changes in pain severity and health-related quality of life over time (P ≤ .001), indicating clinical utility. CONCLUSIONS:Our findings highlight the heterogeneity of cLBP and suggest that tailored treatments targeting these distinct subgroups could improve clinical outcomes. This work advances our understanding of cLBP by providing a robust framework for identifying patient subgroups based on biobehavioral characteristics. Results underscore the value of LPA in uncovering clinically meaningful patterns in complex conditions like cLBP, paving the way for more personalized treatment approaches.

OBJECTIVE:Chronic low back pain (cLBP) is a common condition that impacts quality of life and function. There are many evidence-based treatments to address cLBP; however, treatment effects are modest, perhaps in part due to individual variation in treatment response. The Biomarkers for Evaluating Spine Treatments (BEST) trial was designed as the collaborative centerpiece of the Back Pain Consortium (BACPAC) research program. This consortium was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) as part of the Helping to End Addiction Long-term (HEAL) Initiative. DESIGN:The BEST trial was a sequential multiple assignment randomized trial (SMART) designed with the primary goal of identifying in whom different treatments show optimal response. The primary focus of the study was to use patient features, including biomarkers and phenotypic measures, to identify subsets of persons with cLBP who respond best to specific common treatments. METHODS:Four interventions were chosen for the trial: Enhanced Self-Care, Acceptance and Commitment Therapy, Duloxetine, and Evidence-Based Exercise and Manual Therapy. Following a run-in period and baseline assessment, participants were randomized to 1 of the 4 treatments for the first 12-week intervention period. Participants were reassessed and based on their self-reported response to initial treatment, continued that initial treatment, were augmented with an additional randomly assigned treatment, or were switched to a new treatment. CONCLUSION:This trial was designed to deliver rich phenotypic data that will both potentially aid in the discovery of phenotypic characteristics that predict treatment response and provide a greater mechanistic understanding of cLBP. CLINICAL TRIAL REGISTRATION NUMBER:The Biomarkers for Evaluating Spine Treatments (BEST) trial is registered on ClinicalTrials.gov (Registration number: NCT05396014; https://clinicaltrials.gov/study/NCT05396014).

BACKGROUND:Research suggest that mind-body movement programs have beneficial effects on cognitive outcomes for older adults with cognitive decline. However, few studies have directly compared specific approaches to mind-body movement or studied the impact of remote program delivery. METHODS:In a 3-arm randomized controlled trial (RCT) for older adults with cognitive impairment, we are comparing a multidomain mind-body program that emphasizes movement, body awareness, personal meaningfulness, and social connection, and a traditional Chinese mind-body exercise (Tai Chi) to a health and wellness education control condition. All 3 interventions are delivered remotely two times per week (onehour per session) for 12 weeks. The two active interventions are live-streamed. Outcomes are assessed prior to, after, and 6-months after the interventions. The co-primary outcomes are changes on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) and brain functional connectivity in the Default Mode Network (DMN). Secondary outcomes include measures of specific cognitive domains (e.g., executive function, attention), mobility, and self-report measures of general well-being, quality of life, social engagement, self- and attention-regulation. CONCLUSION:This RCT will directly compare the effects of two mind-body movement programs versus an education control delivered remotely over 12 weeks on cognitive, neuroimaging, and participant-reported outcomes. If successful, these programs may provide scalable strategies for slowing cognitive decline, which could potentially delay dementia onset in some individuals. TRIAL REGISTRATION ID:NCT05217849.

Background: The emerging paradigm of whole person health shares many core principles with traditional complementary and integrative health frameworks, including Tai Chi and Qigong (TCQ). Methods: In the fall of 2023, the Harvard Medical School Osher Center for Integrative Health hosted the inaugural international conference on The Science of Tai Chi & Qigong for Whole Person Health: Advancing the Integration of Mind-Body Practices into Contemporary Healthcare at Harvard Medical School. A two-part white paper was written to summarize key conference topics, findings, and issues. Results and Discussion: Part II presented here summarizes evidence gaps and future research opportunities, including: understudied clinical conditions and populations, impact of long-term TCQ training, understanding the impact of specific TCQ styles, training regimens, dosage, and contextual effects; implementation, cost-effectiveness, and medical utilization research; individual data meta-analysis, and teaching competencies, credentialing, and licensure. Part I of this white paper discusses the rationale for the conference, synthesizes the state of evidence for TCQ as rehabilitative and preventive tools for a range of clinical conditions, and summarizes the translational research informing therapeutic mechanisms associated with TCQ training.

With his elegant studies, Bud Craig determined the structural neural basis for interoception and critically expanded our conceptual understanding of it. Importantly, he placed pain in the framework of interoception and redefined pain as a homeostatic emotion. Craig understood emotions and pain as experiences based on inferential brain processes within the theoretical model of prediction processing. This chapter aims to give a brief overview of relevant research. Mind-body therapies, such as meditation, mindfulness, yoga, Tai Chi, and others, are included as first-line non-pharmacological approaches in clinical guidelines for the management of chronic pain. Craig's groundbreaking work provided the background for our contemporary understanding of mind-body therapies and for the key role that interoceptive processes play in these therapies as they apply to a wide range of clinical conditions, including pain. This chapter reviews the tremendous influence that Craig's work had on the current state of research on mind-body therapies for managing chronic pain and how it led to new directions for cutting-edge clinical and neuroscientific research.

BACKGROUND CONTEXT:There are a number of risk factors- from biological, psychological, and social domains- for nonspecific chronic low back pain (cLBP). Many cLBP treatments target risk factors on the assumption that the targeted factor is not just associated with cLBP but is also a cause (ie, a causal risk factor). In most cases this is a strong assumption, primarily due to the possibility of confounding variables. False assumptions about the causal relationships between risk factors and cLBP likely contribute to the generally marginal results from cLBP treatments. PURPOSE:The objectives of this study were to a) using rigorous confounding control compare associations between modifiable causal risk factors identified by Mendelian randomization (MR) studies with associations in a cLBP population and b) estimate the association of these risk factors with cLBP outcomes. STUDY DESIGN/SETTING:Cross sectional analysis of a longitudinal, online, observational study. PATIENT SAMPLE:A total of 1,376 participants in BACKHOME, a longitudinal observational e-Cohort of U.S. adults with cLBP that is part of the NIH Back Pain Consortium (BACPAC) Research Program. OUTCOME MEASURES:Pain, Enjoyment of Life, and General Activity (PEG) Scale. METHODS:Five risk factors were selected based on evidence from MR randomization studies: sleep disturbance, depression, BMI, alcohol use, and smoking status. Confounders were identified using the ESC-DAG approach, a rigorous method for building directed acyclic graphs based on causal criteria. Strong evidence for confounding was found for age, female sex, education, relationship status, financial strain, anxiety, fear avoidance and catastrophizing. These variables were used to determine the adjustment sets for the primary analysis. Potential confounders with weaker evidence were used for a sensitivity analysis. RESULTS:Participants had the following characteristics: age 54.9±14.4 years, 67.4% female, 60% never smokers, 29.9% overweight, 39.5% obese, PROMIS sleep disturbance T-score 54.8±8.0, PROMIS depression T-score 52.6±10.1, Fear-avoidance Beliefs Questionnaire 11.6±5.9, Patient Catastrophizing Scale 4.5±2.6, PEG 4.4±2.2. In the adjusted models, alcohol use, sleep disturbance, depression, and obesity were associated with PEG, after adjusting for confounding variables identified via a DAG constructed using a rigorous protocol. The adjusted effect estimates- the expected change in the PEG outcome for every standard deviation increase or decrease in the exposure (or category shift for categorical exposures) were the largest for sleep disturbance and obesity. Each SD increase in the PROMIS sleep disturbance T-score resulted in a mean 0.77 (95% CI: 0.66, 0.88) point increase in baseline PEG score. Compared to participants with normal BMI, adjusted mean PEG score was slightly higher by 0.37 points (95% CI: 0.09, 0.65) for overweight participants, about 0.8 to 0.9 points higher for those in obesity classes I and II, and 1.39 (95% CI: 0.98, 1.80) points higher for the most obese participants. Each SD increase in the PROMIS depression T-score was associated with a mean 0.28 (95% CI: 0.17, 0.40) point increase in baseline PEG score, while each SD decrease in number of alcoholic drinks per week resulted in a mean 0.12 (95% CI: 0.01, 0.23) increase in baseline PEG score in the adjusted model. CONCLUSIONS:Several modifiable causal risk factors for cLBP - alcohol use, sleep disturbance, depression, and obesity- are associated with PEG, after adjusting for confounding variables identified via a DAG constructed using a rigorous protocol. Convergence of our findings for sleep disturbance, depression, and obesity with the results from MR studies, which have different designs and biases, strengthens the evidence for causal relationships between these risk factors and cLBP. The estimated effect of change in a risk factor on change in PEG were the largest for sleep disturbance and obesity. Future analyses will evaluate these relationships with longitudinal data.

Background: The emerging paradigm of whole person health shares many core principles with traditional complementary and integrative health frameworks, including Tai Chi and Qigong (TCQ). Methods: In the Fall of 2023, the Harvard Medical School Osher Center for Integrative Health hosted the inaugural international conference on The Science of Tai Chi & Qigong as Whole Person Health: Advancing the Integration of Mind-Body Practices into Contemporary Healthcare held at Harvard Medical School. A two-part white paper was written to summarize key conference topics, findings, and issues. Results and Discussion: Part I presented here summarizes the rationale for the conference and synthesizes the state of evidence for TCQ as rehabilitative and preventive tools for a range of clinical conditions, including falls and balance, cognition, mental health, sleep, cardiorespiratory health, musculoskeletal health, cancer, as well as translational evidence related to the neurophysiology, brain and immune function, and biomarkers of inflammation. The state of science of TCQ, viewed through the lens of traditional East Asian health constructs, is also discussed. Part II of this white paper outlines evidence gaps and opportunities and discusses strategies to address challenges in TCQ research, dissemination, and implementation.

Mindfulness meditation training may cultivate interoceptive awareness and provide therapeutic benefit when implemented within mental and physical health interventions. This pre-registered meta-analysis evaluated the impact of mindfulness interventions on self-reported interoception measures and associated relationships with psychological outcomes. Twenty-nine randomized controlled trials with 2,191 participants (77.8% female, mean age 32.8 years) were meta-analyzed using correlated and hierarchical effects models. Interventions included mindfulness-based programs (k = 15), body-based approaches (incorporating elements like massage, k = 8), and other variations (k = 6). Five SIMs were tested; the Multidimensional Assessment of Interoceptive Awareness was the most common (22 studies). Results showed a small-to-medium positive effect on interoception measures across all studies (g = 0.31, p < 0.001, 95% CI [0.21, 0.42]) with low-to-moderate heterogeneity (τ = 0.16). Mindfulness-based programs demonstrated the largest effects (g = 0.41). No evidence of publication bias was found. No other moderators, such as practice dosage or clinical sample, were significant. Improvements in self-reported interoception were similar in size to improvements in self-reported mindfulness and were related to improvements in psychological distress. These meta-analytic findings provide evidence that mindfulness-based interventions lead to adaptive changes in the subjective experience of interoception, perhaps contributing to improved mental wellbeing.

Objective Chronic low back pain (cLBP) is a significant public health problem in the United States. A method to identify treatments that are most likely effective for an individual patient based on their unique characteristics is needed.Methods The Biomarkers for Evaluating Spine Treatments (BEST) Trial is a sequential, multiple assignment, randomized trial designed to estimate an optimal treatment or combination of treatments to reduce pain intensity and interference at 24 weeks in individuals with cLBP.Results We describe the patient-reported characteristics of the BEST Trial at the Baseline visit. Data collection for extensive required phenotyping is reported. We analyzed the run-in period of the BEST Trial to evaluate predictors of run-in failure. The BEST Trial enrolled 1019 participants and randomized 805 participants (61.6% female, mean age 50.4, 12.5% Black or African American) to the first stage of treatment. We collected extensive required phenotyping on all 805 randomized BEST Trial participants, and additional optional phenotyping on 510 (63.4%) participants.Conclusions The BEST Trial successfully enrolled a racially and geographically diverse sample of chronic low back pain patients and completed rich phenotypic assessments to inform our primary goal of identifying in whom different treatments show optimal response. We demonstrated the feasibility of collecting extensive phenotypic assessments in a multi-site clinical trial of cLBP.Clinical trial registration number The Biomarkers for Evaluating Spine Treatments (BEST) Trial is registered on ClinicalTrials.gov. Registration number: NCT05396014 (https://clinicaltrials.gov/study/NCT05396014).

There are no reported randomized trials testing exercise versus an active comparator for Posttraumatic Stress Disorder (PTSD). This randomized clinical trial assessed the effectiveness of group exercise versus psychoeducation to improve quality of life and reduces symptomatic severity in Veterans with PTSD. Veterans who met criteria for current PTSD (DSM-5) and/or endorsed moderate levels of PTSD symptoms (CAPS 5 score ≥ 23) were randomly assigned to treatment. Integrative Exercise (IE) combines fitness exercises (aerobics, resistance training, stretching) with mindful body/breath awareness versus Recovery Class (REC) psychoeducation control condition. A total of 84 participants were enrolled of which 41 participants were randomized to IE and 43 participants to REC. There were no significant pre-post differences in change in the WHOQOL Psychological Domain in either group. There was a modest reduction in the total CAPS-5 score in both groups (IE: -8.2 (9.9), p < .001: REC: -7.8 (2.0), p < .001) but no differences across the two conditions. In the IE subsample that was remote, there was a greater improvement in PTSD symptom severity (F[1, 50] = 4.62, p = .036) and in in the WHOQOL Psychological Domain (F(1, 47) = 6.46, p = .014) in those who attended more sessions. Trial Registration: ClinicalTrials.gov Identifier: NCT02856412 (registration date: February 27, 2017)

Purpose: Mindfulness-Based Stress Reduction (MBSR) has shown efficacy for alleviating chronic low back pain (cLBP) and is included in current treatment guidelines. However, benefits are moderate. We aimed to optimize MBSR for chronic pain by using recent research to develop Mindfulness-Based Pain Reduction (MBPR) and test it in patients with cLBP. Patients and Methods: Phase 1: We modified the MBSR curriculum with theory-driven components and convened focus groups with local and international mindfulness and clinical pain management experts to refine an 8-week MBPR program. Phase 2: We recruited participants with cLBP from Northern California using outreach in newsletters, social media, and other methods to test and iteratively modify the curriculum. MBPR was delivered in a group format by videoconference. The first three groups received MBPR; a fourth group was randomized to MBSR or MBPR to assess randomization feasibility. We assessed feasibility and acceptability by attendance, practice logs, and exit interviews. We assessed changes in patient-reported outcome measures for low back pain trials using a single arm (treatment group only) approach at 2 and 6 months with linear mixed models (primary: pain intensity and interference (PEG) scores). Results: Phase 1: The MBPR curriculum included: 1) mindful interoceptive exposure to pain, 2) pain neuroscience education, and 3) yoga postures specifically for cLBP. Phase 2: we enrolled 58 patients in 4 cohorts; 49 completed post-intervention and 41 completed 6-month follow-up assessments; 29 of the 41 received MBPR. Participants attended a mean of 80% of sessions and 23 of 24 participants accepted randomization in the 4th cohort. Mean PEG scores improved for 20 of 29 MBPR participants in a clinically Conclusion: MBPR was feasible and acceptable. Two-thirds of MBPR participants experienced clinically meaningful improvements in pain intensity and interference scores. MBPR warrants further investigation through a randomized, controlled trial.

AbstractINTRODUCTIONThere are few widely‐available, evidence‐based options to support quality of life (QOL) for people living with Alzheimer's disease and related dementias.METHODSWe performed a randomized, controlled trial with a Waitlist control group to determine whether an online, livestream, mind‐body, group movement program (Moving Together, 1 hour, 2 days/week, 12 weeks) improves QOL in people with cognitive impairment (PWCI) or care partners (CPs) and explore mechanisms of action. The primary outcome for both participants was self‐reported QOL. Secondary outcomes and potential mediators included mobility, isolation, well‐being, cognitive function, and sleep in PWCI and burden, positive emotions, caregiver self‐efficacy, stress management, and sleep in CPs. Blinded assessors collected outcome data at baseline, 12, and 24 weeks. We assessed adverse events including falls through monthly check‐in surveys and collected qualitative data through evaluation surveys. Intention‐to‐treat analyses used linear mixed models to compare mean change over time between groups and calculated standardized effect sizes (ESs).RESULTSNinety‐seven dyads enrolled (PWCI: age 76 ± 11 years, 43% female, 80% non‐Hispanic White; CPs: age 66 ± 12 years, 78% female, 71% non‐Hispanic White); 15% withdrew before 12 weeks and 22% before 24 weeks. PWCI self‐reported significantly better QOL from baseline to 12 weeks in the Moving Together group compared to the Waitlist group (ES = 0.474, p = 0.048) and CPs self‐reported improved ability to manage stress (ES = 0.484, p = 0.021). Improvements in participant self‐reported QOL were mediated by improvements in their self‐reported well‐being and CP‐reported ability to manage stress. Results were similar when the Waitlist group participated in the program (QOL ES = 0.663, p = 0.006; stress management ES = 0.742, p = 0.002) and were supported by qualitative data. Exploratory analyses suggested possible fall reduction in PWCI. There were no study‐related serious adverse events.DISCUSSIONOnline programs such as Moving Together offer a scalable strategy for supporting high QOL for PWCI and helping CPs manage stress.TRIAL REGISTRATIONClinicalTrials.gov NCT04621448Highlights The approval of new medications that slow cognitive decline in people living with Alzheimer's disease and related disorders (ADRD) has raised hope and excitement. However, these medications do not appear to impact quality of life, which is often considered by patients and care partners to be the most important outcome. In this randomized clinical trial, we found that an evidence‐based, online, livestream, mind‐body, group movement program significantly and meaningfully improves self‐rated quality of life in people with ADRD and helps care partners manage stress. Mediation analyses revealed that the key drivers of improvements in participants’ quality of life were improvements in their feelings of well‐being and care partners’ ability to manage stress. Exploratory analyses also suggested a 30% reduction in falls. These results are important because they suggest that an online program, which is available now and can be performed by people from the comfort of home or other location of choice, could be recommended as a complement or alternative to new therapies to help maximize quality of life for people living with ADRD and their care partners.

Introduction:Chronic low back pain (cLBP) is highly prevalent in the United States and globally, resulting in functional impairment and lowered quality of life. While many treatments are available for cLBP, clinicians have little information about which specific treatment(s) will work best for individual patients or subgroups of patients. The Back Pain Research Consortium, part of the National Institutes of Health Helping to End Addiction Long-termSM (HEAL) Initiative, will conduct a collaborative clinical trial, which seeks to develop a personalized medicine algorithm to optimize patient and provider treatment selection for patients with cLBP. Objective:The primary objective of this article is to provide an update on evidence-based cLBP interventions and describe the process of reviewing and selecting interventions for inclusion in the clinical trial. Methods:A working group of cLBP experts reviewed and selected interventions for inclusion in the clinical trial. The primary evaluation measures were strength of evidence and magnitude of treatment effect. When available in the literature, duration of effect, onset time, carryover effect, multimodal efficacy, responder subgroups, and evidence for the mechanism of treatment effect or biomarkers were considered. Conclusion:The working group selected 4 leading, evidence-based treatments for cLBP to be tested in the clinical trial and for use in routine clinical treatment. These treatments include (1) duloxetine, (2) acceptance and commitment therapy, (3) a classification-based exercise and manual therapy intervention, and (4) a self-management approach. These interventions each had a moderate to high level of evidence to support a therapeutic effect and were from different therapeutic classes.

BACKGROUND CONTEXT Chronic low back pain (cLBP) is a major global cause of disability, with health care costs exceeding $100 billion annually in the US. Its treatment poses a complex challenge due to the interplay of biological, psychological, and social factors. Understanding the diversity of cLBP is crucial for effective treatment, especially precision medicine for nonspecific cLBP. Unsupervised clustering methods have been increasingly used for patient phenotyping, yet the outcomes and interpretations of these methods heavily depend on the implementation and decisions made during analysis. PURPOSE Utilizing multimodal data from a cLBP prospective cohort, our aim was to systematically evaluate different clustering algorithms for unsupervised patient phenotyping. We critically assessed the effectiveness and reliability of these algorithms in our analysis. STUDY DESIGN/SETTING N/A PATIENT SAMPLE N/A OUTCOME MEASURES N/A METHODS We analyzed multimodal data (demographics, clinical characteristics, imaging, biomechanics, and psychosocial factors) from a preliminary 244 participants in the UCSF ComeBACK cohort study, collected between 2019 to 2023. After consulting domain experts, 679 variables were selected, and missing value imputation was performed. The data underwent dimensional reduction using Multiple Factor Analysis (MFA) or Isometric Mapping (ISOMAP). Systematic clustering algorithms applied included K-means (KM), Fuzzy K-means (Fuzzy), Agglomerative Clustering (AGC), Gaussian Mixture Model (GMM), Bayesian Gaussian Mixture Model (BGMM), and Spectral Clustering (SPC). After grid search for number of clusters (2-10), we plotted gap statistics (GAP) and silhouette scores (SS), two distinct metrics of clustering performance, exploring optimal cluster numbers and evaluating findings. RESULTS Visually, common clustering tendencies across different algorithms were observed. Specifically, a commonality around 6 clusters was noted, with shared clusters identifiable in 6 regions (top, right, center, top-left, bottom-left, and bottom) of the plot, except for AGC. Subsequently, the effectiveness of systematic cluster metrics was calculated. Both GAP and SS, metrics considering the density within clusters and separation between clusters, were used to measure clustering quality. The inflection point where the increase in GAP values slows down indicates the appropriate number of clusters, while higher SS signify better cluster separation and cohesion. A common trend was observed across both MFA and ISOMAP processed data for each metric. Particularly in ISOMAP, for KM, GMM, and SPC, a slight inflection point around 6 clusters was noted, supporting the visual observations from the scatter plots. Also, multiple algorithms showed an increase in SS around 6-7 clusters. However, inconsistencies between the metrics were noted; while SS consistently indicated optimal separation at two clusters, GAP suggested differently. CONCLUSIONS This analysis revealed both variations and common trends dependent on clustering algorithms and evaluation metrics, underscoring the importance of systematic and comprehensive method application for robust analysis. Furthermore, in this data, both visual observations and clustering metrics suggested that clusters of sizes 2 and 6-7 could represent significant data structures. Building on this foundational analysis, the next step will focus on creating robust clusters using ensemble clustering and assessing their clinical relevance. FDA Device/Drug Status This abstract does not discuss or include any applicable devices or drugs.

IntroductionChronic low back pain (cLBP) poses significant challenges, often addressed through avoidance or distraction. Emerging evidence suggests that mind-body interventions, like our novel Mind Your Pain (MyP) smartphone mobile application, may offer relief. We conducted a single-arm, mixed-methods neuroimaging study to assess the degree to which treatment response to our 8-week intervention, as measured by the reduction in the Pain, Enjoyment of Life and General Activity Scale (PEG), was associated with enhanced pain-related insula activation over time.MethodsTwenty-nine individuals with cLBP completed patient-reported assessments, qualitative sensory testing (QST) measures, and neuroimaging pre- and post-MyP. Functional MRI data during experimental heat pain on the left forearm were collected and analyzed, comparing responders (≥50% reduction in PEG scores) and non-responders.ResultsMyP led to significant decreases in PEG scores overall. Furthermore, MyP responders exhibited increased pain-related activation in key brain regions, including the contralateral posterior insula, bilateral ventral anterior insula, ventral anterior cingulate, dorsolateral prefrontal cortex, and nucleus accumbens. Although baseline behavioral and sensory measures did not differ between the two responder groups, baseline neural differences related to the impact of the endogenous back pain were observed.DiscussionMyP appears to modify pain response and underlying neural circuitry, suggesting neural changes in interoception may serve as biomarkers for mind-body interventions in cLBP. This study highlights the potential of MyP as a novel approach for cLBP management, warranting further investigation.

Context Interoceptive bodily awareness (IBA) is one's attentional focus on and relationship with comfortable and uncomfortable (e.g., pain) internal body sensations. Integrating IBA into research on osteopathic manipulative treatment (OMT) is growing, both as an outcome and predictor of treatment outcomes; however, it has yet to be studied in a clinical setting. Objectives We aimed to conduct a pilot study to measure IBA, with the Multidimensional Assessment of Interoceptive Awareness (MAIA), in patients seeking OMT for pain, and to test if OMT exposure may be associated with higher IBA as measured by the MAIA. The primary outcome was the change in MAIA scores, and the secondary outcomes were reduction in pain intensity, reduction in pain interference, and increase in participants' perception of change post-OMT. Methods A convenience sample was recruited from individuals presenting for OMT appointments at a College of Osteopathic Medicine OMT teaching clinic. Participants were recruited into our single-arm observational cohort study (n=36), and categorized into one of two groups, OMT-na & iuml;ve (n=19) or OMT-experienced (n=17), based on prior exposure to OMT. We measured MAIA scores and clinical pain-related outcomes prior to, immediately after, and at 1 and 3 weeks after a usual-care OMT session in the clinic. Covariates including experience with mind-body activities, non-OMT body work, and physical and emotional trauma were also collected to explore potential relationships. We utilized t tests to compare MAIA scores and pain outcomes between groups and across time points. Stepwise regression models were utilized to explore potential relationships with covariates. Results The OMT-experienced group scored higher on the MAIA scales "Not-worrying" (p=0.002) and "Trusting" (p=0.028) at baseline. There were no significant changes in the MAIA scores before and after the single OMT session. Analysis of secondary outcomes revealed that all pain outcomes significantly decreased post-OMT (p<0.05), with the largest relative improvements in the acute pain and OMT-na & iuml;ve subgroups, with diminishing effects over time. Conclusions Assessing IBA with MAIA in a clinical OMT setting is feasible. There were significant positive correlations between OMT exposure and two of the eight MAIA scales. Future studies are justified to further explore this relationship.

INTRODUCTION:Understanding individual patient preferences for chronic low back pain (cLBP) outcomes is essential for targeting available therapeutic options; yet tools to elicit patient outcome preferences are limited. OBJECTIVE:To develop and test a choice-based conjoint (CBC) measure, commonly used in behavioral economics research, to elicit what outcomes patients with cLBP want to achieve and avoid. DESIGN:We developed a survey-based CBC measure to allow patients to make risk/benefit trade-off choices between possible treatment outcomes. After extensive literature, clinician, and patient input, our measure included seven attributes: fatigue, anxiety/depression, difficulty thinking/making decisions, pain intensity, physical abilities, change in pain, and ability to enjoy life despite pain. Random-parameters logit models were used to estimate strength of preferences, and latent class analysis was used to identify patient characteristics associated with distinct preference. SETTING:Online study using the Sawtooth web-based platform. PARTICIPANTS:Two hundred eleven individuals with cLBP recruited from online advertising as well as at clinical sites across multiple academic and private institutions. INTERVENTIONS:Not applicable. RESULTS:The most valued outcome was the highest level of physical activity (β = 1.6-1.98; p < .001), followed by avoiding cognitive difficulties (β = -1.48; p < .001). Avoidance of severe pain was comparable to avoiding constant fatigue and near-constant depression/anxiety (β = -0.99, -1.02); p < .001). There was an association between preferences and current pain/disability status; patients with higher pain had a stronger preference to avoid severe pain, whereas those with higher disability have stronger preferences for achieving physical activity. The latent class analysis identified two distinct groups: (1) more risk-seeking and willing to accept worse outcomes (56%); and (2) more risk-averse with a stronger preference for achieving maximum benefits (44%). CONCLUSIONS:Our study illuminated cLBP patient preferences for treatment outcomes and heterogeneity in these preferences. Patients stressed the importance of reaching high physical activity and avoiding cognitive declines, even over a desire to avoid pain. More work is needed to understand patient preferences to aid informed, shared decisions.

OBJECTIVE:People commonly cope with chronic low back pain (cLBP) by ignoring and distraction. Can mindful interoceptive exposure to the pain sensation itself and its phenomenological components be an alternative approach? METHODS:Single-arm feasibility study in patients with cLBP using a 2-minute attention exercise guided by a smartphone app several times per day over 8 weeks. We assessed feasibility, pre/post pain, function, and psychological parameters using mixed methods: standard questionnaires, ecological momentary assessment, and exit interviews that included micro-phenomenology technique and subsequent reflexive thematic qualitative analysis. RESULTS:We enrolled 31 participants, mostly female, mean age 48, the majority had pain for >5 years; 29 completed. Mean pain intensity [0-10] improved from 4.8 ±1.7 to 3.1 ±1.9 (p < .0001); mean PEG scores (intensity and interference with daily life; range 0-30) improved from 13.7 ±6.2 to 8.4 ±6.6 (p < .0001); pain impact (9 items incl physical function) 22.3 ±8.7 to 19.7 ±8.1 (p = .0010). Twenty-one of 29 improved PEG score ≥30%. There were significant improvements in PCS Rumination and MAIA Not-Worrying. Participants became aware of their usual habit of avoidance and the challenge of and resistance to focusing on pain. They were surprised how pain sensations varied over time, and that pain intensity and the threat value of pain could diminish by focusing on it. They described a variety of 3D pain shapes (e.g., football, pool ball, rod, nail, brick, stars) with a range of colors, transparency, temperature, and density that for some changed with mindful attention. Most struggled to find appropriate words for sensory awareness and attention regulation and found that the threat value of their pain diminished. CONCLUSIONS:Mindful interoceptive exposure to the sensations of their cLBP using a 2-minute attention exercise with a phone app-rather than ignoring and distracting from it-may be a beneficial intervention for cLBP. TRIAL REGISTRATION:ClinicalTrials.gov #NCT06186193.