Importance:The increasing cost of lumbar fusion has invited payment reforms, such as mandatory price limits by Medicare in 2026. Objective:To examine the cost, utilization, and procedural case-mix trends for different types of lumbar fusion from 2002 to 2023 in the United States. Design, Setting, and Participants:This cross-sectional analysis used survey-weighted data from the 2002 to 2023 National Inpatient Sample (NIS) and the 2016 to 2022 Nationwide Ambulatory Surgical Sample (NASS). From this nationally representative sample of inpatient and hospital-owned outpatient discharges, information on US adults aged 20 years and older undergoing lumbar fusion for any indication from January 2002 to December 2023 were included. Exposures:Lumbar fusion of any type (1-disc level or multilevel as well as single vertebral column or both anterior-posterior columns) with nonfusion surgery as a comparison. Main Outcomes and Measures:The main outcomes were the survey-weighted annual total of procedures, the mean age of patients undergoing lumbar fusion, the inflation-adjusted hospital costs, and the annual procedure rates per 100 000 population. Results:A total of 5 033 772 lumbar fusion admissions between 2002 and 2023 were included. In 2023, the cohort of patients undergoing 274 750 procedures had a mean (SD) age of 63.2 (12.9), with 142 815 (52.0%) female patients. Excluding 54 620 complex fusions, which were mostly multilevel anterior-posterior column fusions, there were 164 105 (50.1%) multilevel fusions, and 109 130 (51.3%) combined anterior-posterior column fusions. The age-adjusted population rate of inpatient fusion procedures increased from 60.1 (95% CI, 58.8-90.3) per 100 000 in 2002 (148 823 admissions) to a peak of 89.9 (95% CI, 89.6-90.3) in 2016 (284 180 admissions), before declining to 80.0 (95% CI, 79.7-80.4) by 2023 (273 235 admissions). Lumbar fusion performed in hospital-owned outpatient facilities was minimal in 2016 (6132 procedures, or 2.1% of total lumbar fusions) and 6.9 per 100 000 (27 331 procedures, or 9.8% of total lumbar fusions) in 2022. Adjusted inpatient hospital costs increased 265.3% from $3.86 (95% CI, $3.81-$3.92) billion in 2002 to $14.1 (95% CI, $13.9-$14.2) billion in 2023, and mean inpatient per-procedure cost increased from $25 849 (95% CI, $25 684-$26 015) in 2002 to $45 458 (95% CI, $45 207-$45 709) in 2023. Lumbar fusion primarily shifted from single column at 1 or 2 disc levels in 2002 (mean cost, $24 515; 95% CI, $24 361-$24 669) to multilevel anterior-posterior column fusion in 2023 (mean cost, $55 034; 95% CI, $54 420-$55 650). Conclusions and Relevance:In this cross-sectional study, lumbar fusion trends were marked by greater utilization of procedures overall, and especially involving multilevel and combined anterior-posterior column approaches and by greater use in the outpatient setting. Costs also increased at both the national and per-procedure levels.

OBJECTIVE:This study aimed to (1) compare networks of factors for patients with low and high recovery expectations in individuals with lumbar spinal stenosis (LSS) using biopsychosocial measures and duration of symptoms and (2) identify the most influential factors within each group. METHODS:We conducted a cross-sectional study using baseline data from 598 patients with LSS. Participants were recruited through Duke University and the University of Washington spine clinics between 2021 and 2024. Recovery expectations were assessed using a 0 (lowest) to 10 (highest) numerical rating scale. We stratified participants into low and high expectation groups. Network analysis was used to assess relationships among factors for each group. Networks included chronicity and PROMIS-29 + 2 Profile. Partial correlations, centralities, network comparison measures, and network stabilities were calculated. RESULTS:There were 226 participants with low and 108 with high recovery expectations. The 2 networks did not have significant structural differences, and strength centralities were stable. Chronicity was not significantly associated with other factors in both networks. Pain Interference and Fatigue strength centralities show greater importance in both networks. Anxiety had significantly higher strength in the low expectation group, suggesting greater relevance for individuals with low expectations. CONCLUSION:Pain Interference and Fatigue were influential for both groups, while Anxiety was more influential for those with low expectations. Future research and patient management should consider the influence of anxiety for those with low recovery expectations and pain interference and fatigue for all individuals with LSS on other associated factors.

Introduction:Without valid inclusion of concurrent analgesic use, the primary analyses of pain intensity in pain randomized controlled trials (RCTs) may produce diminished estimated treatment effects. Methods:We used contemporary causal inference methods to reanalyze RCT data examining the effect of epidural steroid injection (ESI) as an example of a pain treatment. Specifically, we define an "attributable to ESI estimand," which is the controlled direct effect of ESI. We used a simple composite pain intensity outcome, the QPAC1.5, and structural mean models (SMM) to estimate the target estimand. Compared with traditional methods such as strict intention to treat analysis (strict ITT), SMMs can account for analgesic use without assuming no unmeasured confounding between the analgesic use and the outcome. We estimated treatment effects of ESI on leg pain intensity using the numeric rating scale with strict ITT, 3 SMM estimating methods (estimating equations, g-estimation, and generalized method of moments), and the QPAC1.5. Results:The treatment effect of ESI on leg pain intensity using strict ITT was -0.751 numeric rating scale points (95% confidence interval [CI]: -1.287 to -0.214). Estimates for the attributable to ESI estimand were -0.864 (95% CI: -3.207 to 1.478) for estimating equations, -0.935 (95% CI: -1.779 to 0.090) for g-estimation, -0.653 (95% CI: -1.218 to -0.089) for generalized method of moments, and -0.930 (95% CI: -1.508 to -0.352) for the QPAC1.5. Discussion:We illustrate how contemporary causal inference methods and alternative estimands can be used to account for concurrent analgesic use in pain RCTs in a manner that may result in larger treatment effects.

OBJECTIVE:This study describes the enrollment and baseline characteristics of participants in the Lumbar Stenosis Prognostic Subgroups for Personalizing Care and Treatment Study (PROSPECTS) cohort and explores subgroups of patients presenting for nonoperative care. DESIGN:Cross-sectional study. SETTING AND SUBJECTS:We enrolled adults ≥50 years of age initiating nonoperative care for symptomatic lumbar spinal stenosis. We excluded those with serious spinal pathology, conditions limiting ambulation, and prior or planned lumbar surgery. METHODS:We collected demographics, the Patient-Reported Outcomes Measurement Information System (PROMIS) 29, pain intensity, Oswestry Disability Index, Swiss Spinal Stenosis Questionnaire, chronicity of symptoms, pain sites, comorbidities, falls, and opioid use. We used descriptive statistics to characterize the sample and latent class analysis to derive subgroups with distinct phenotypes. The best model was selected on the basis of model fit statistics, class separation, and clinical interpretability. RESULTS:We enrolled 598 participants. The mean age was 67 (SD = 9), and 61% were female. Back and leg pain had been present for ≥1 year in 65% of participants. Multiple pain sites were common, with a mean of 4.3 sites (SD = 2.2), and a majority of patients had multiple comorbidities (54%). We selected a 4-class solution as the best model from the latent class analysis. These phenotypes were described as (1) "high pain impact, low psychosocial features" (n = 233; 39%), (2) "mild pain impact, low psychosocial features" (n = 218; 36%), (3) "high pain impact, complex health needs" (n = 95; 16%), and (4) "acute, intermittent, moderate-severe leg pain with high pain impact" (n = 52; 9%). CONCLUSIONS:These phenotypes reflect distinct profiles that could inform health needs and patient-centered care. Future studies should examine longitudinal outcomes to establish their clinical utility and prognostic value.

Exacerbations of existing low back pain (LBP) or new LBP episodes are colloquially referred to as "flares." Although the experience of flares is common to many people with LBP, few validated measures enable people to self-report if they are experiencing a flare. This study examined the convergent validity of a person-dependent definition of flares ("a worsening of your low back pain that lasts from hours to weeks") as compared with (1) LBP intensity, (2) LBP-related pain interference, and (3) analgesic use, in a large, prospective research study of Veterans with LBP. Veterans seeking care for LBP (n = 465) were followed prospectively for up to 1 year. Participants completed up to 36 scheduled surveys and additional patient-initiated surveys (triggered by the onset of new flares) over follow-up. Each survey inquired about current flare status, pain intensity measured on a 0 to 10 numeric rating scale (NRS), LBP-related pain interference, and analgesic use. Linear mixed-effects models estimated the association between current flare status and pain intensity, with and without adjustment for potential confounding factors; secondary analyses examined associations with pain interference and analgesic use. In longitudinal analyses of 11,817 surveys, flare status was significantly associated with a 2.8-NRS point greater pain intensity (P < 0.0001), with and without adjustment for other factors. Statistically significant associations were found between flare status and LBP-related pain interference and analgesic use. New flare periods were associated with impacts on coping, functional limitations, and mood/emotions. These findings support the convergent validity of a person-dependent flare definition.

BACKGROUND CONTEXT Most patients with symptomatic lumbar spinal stenosis (LSS) initially receive nonoperative care before considering surgery, but there is limited high-quality evidence on the overall prognosis of patients seeking nonsurgical care to guide decision making. PURPOSE 1) Describe the clinical course of outcomes over 12 months among patients with LSS who are initiating nonoperative care and 2) examine if patients’ trajectories differ by age, sex, and duration of symptoms. STUDY DESIGN/SETTING Inception cohort study over 12 months at 2 sites. PATIENT SAMPLE We enrolled patients ≥50 years with symptomatic LSS who were initiating nonoperative care in secondary settings. We excluded patients: 1) with serious medical conditions that may produce back-related symptoms or limit walking, 2) who had prior lumbar spine surgeries, and 3) who were planning on lumbar surgery. OUTCOME MEASURES We collected the Oswestry Disability Index (ODI), leg pain intensity using an 11-point numerical rating scale, and the Swiss Spinal Stenosis Questionnaire (SSSQ) symptoms and function subscales via electronic survey or telephone at baseline and 3, 6, and 12 months. METHODS We collected demographics and health characteristics at baseline, including age, sex, and duration of LSS symptoms. We described outcomes at all time points and used linear mixed-effects models to test if the trajectory of each outcome differed by age group (50-59, 60-69, 70-79, and ≥80), sex, and duration of LSS symptoms (<3 months, 3-6 months, 6-12 months, 1-5 years, and > 5 years). We included an interaction term with time to determine if change over time differed by group. Models were adjusted for age, sex, duration, study site, race, education, marital status, and employment status accordingly. RESULTS This analysis included 519 participants who reached their 12-month follow-up. The mean age was 67 (SD=9), and 61% were female. A plurality of participants (37%) had symptoms for > 5 years, and 6% reported lumbar spine surgery over 12 months. On average, the ODI decreased at each time point from 34 (SD=16) at baseline to 26 (SD=18) at 12 months. Mean leg pain scores decreased from 5.4 (SD=4.4) at baseline to 3.8 (SD=2.6) at 6 months and then remained stable to 12 months. The SSSQ symptoms and function subscales also decreased from baseline (3.2 [SD=0.7] and 2.2 [SD=0.7], respectively) to 6 months (2.3 [SD=0.7] and 1.8 [SD=0.6], respectively) and then remained stable. The mixed-effects models showed age was not associated with ODI, leg pain, SSSQ function scores at any timepoint. However, those ≥80 years had higher SSSQ symptom scores at 6 months vs those 50-59, and there was a significant age by time interaction (p=0.0001). There was no difference by sex for ODI scores, leg pain intensity, and SSSQ subscale scores at all timepoints and no significant sex by time interactions. Patients with symptoms < 3 months and 3-6 months had significantly lower ODI, leg pain, and SSSQ subscale scores at 3, 6, and 12-months vs those with > 5 years of symptoms. The duration by time interaction term was significant (p<0.0001) for each outcome. CONCLUSIONS This large cohort of patients seeking non-operative care for LSS showed, on average, patients improved over 12 months. Back-related disability steadily declined over 12 months. Leg pain, stenosis symptoms, and stenosis-related function improved most over the first 6 months. Patients with symptoms lasting ≤6 months had substantially greater improvement over time compared to those with > 5 years of symptoms. FDA Device/Drug Status This abstract does not discuss or include any applicable devices or drugs.

To examine associations between lumbar intervertebral disc degeneration (LDD) and type II Modic changes (MC) when retaining information at each interspace (“interspace-level analysis”), as compared to aggregating information across interspaces as is typically done in spine research (“person-level analysis”). The study compared results from (1) interspace-level analyses assuming a common relationship across interspaces (the “interspace-level, common-relationship” approach), (2) interspace-level analyses allowing for interspace-specific associations (an “interspace-level, interspace-specific” approach), (3) and a conventional person-level analytic approach. Adults in primary care (n = 147) received lumbar spine magnetic resonance imaging and neuroradiologist-evaluated assessments of prevalent disc height narrowing (DHN), type II MC, and other LDD parameters. Analyses examined associations between DHN and type II MC in interspace-level, common-relationship analyses, interspace-level, interspace-specific analyses, and conventional person-level analyses. Cross-sectional, interspace-level, common-relationship analyses found large-magnitude DHN-type II MC associations (adjusted OR [aOR] = 6.5, 95

BACKGROUND CONTEXT:Recent work indicates no increased mortality risk with concurrent gabapentin and opioid use when using an active comparator control design. However, concurrent gabapentin and opioid prescriptions have been associated with greater risk of respiratory depression in some studies. PURPOSE:To compare the risk of respiratory events among Medicare enrollees with histories of spine-related diagnoses treated with gabapentin+opioids versus those treated with tricyclic antidepressants (TCA) or duloxetine+opioids. We hypothesized that enrollees treated with gabapentin+opioids would have increased risk of adverse respiratory events compared to those treated with an active control+opioids. STUDY DESIGN/SETTING:Propensity score-matched cohort study with an incident user, active comparator (TCA/duloxetine) control design. The primary analysis included those who concurrently (within 30 days) filled ≥1 incident gabapentin+≥1 opioid or ≥1 incident TCA/duloxetine+≥1 opioid prescription. PATIENT SAMPLE:US Medicare beneficiaries with histories of spine-related diagnoses 2017 to 2019. People treated with gabapentin+opioids (n=66,860) were matched on demographic and clinical factors to people treated with TCAs/duloxetine+opioids (n=66,860). OUTCOME MEASURES:Time to a composite respiratory outcome consisting of mechanical ventilation, intubation, respiratory failure, pneumonia, or acute respiratory distress syndrome. METHODS:Cox proportional hazard regression was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). RESULTS:Among 133,720 Medicare enrollees (median age 73.3 years; 66.9% female), 6277 (4.7%) experienced respiratory events before the end of follow-up. A total of 3,469 (5.2%) of people who were treated with gabapentin+opioids (median initial dose/day of gabapentin was 300 mg) had respiratory events compared to 2808 (4.2%) of those treated with an active control+opioids. The increased risk in those treated with gabapentin+opioids was statistically significant after adjustment (HR 1.19; 95% CI 1.13, 1.25; p<.0001). The most common respiratory events were pneumonia (3.7% of people in the gabapentin+opioids group versus 3.0% of people in the TCA/duloxetine+opioids group) and respiratory failure (2.3% in the gabapentin+opioids group versus 1.8% in the TCA/duloxetine+opioids group). Results were similar in analyses (a) restricted to ≤30-day follow-up and (b) that required ≥2 fills of each prescription. CONCLUSIONS:While recent work indicates no increased mortality risk with concurrent gabapentin and opioid use in this population, the current findings suggest clinicians should exercise caution in prescribing gabapentin to older adults with spine conditions who are using opioids, due to possible impacts on respiratory events. However, we cannot be certain that unmeasured confounding may explain these results and replication is needed.

Introduction:Back pain (BP) is a complex heritable trait with an estimated heritability of 40% to 60%. Less than half of this can be explained by known genetic variants identified in genome-wide association studies.Objectives:We applied a powerful multi-trait and gene-based approach to association analysis of BP to identify novel genes associated with BP.Methods:Using phenotypes and imputed genotypes from the UK Biobank 500k dataset, we generated a multi-trait phenotype by combining 3 BP-related phenotypes: chronic BP, dorsalgia, and intervertebral disk disorders. We performed gene-based association analysis for 3 BP-related phenotypes and multi-trait phenotype. Conditional analysis was applied to account for the effects of genetic variants outside the gene. Finally, we replicated significantly associated genes using the FinnGen database.Results:We identified 32 genes associated with BP and replicated 16 of them. Thirteen genes were detected using the multi-trait phenotype. Seven of the detected genes, MIPOL1, PTPRC, RHOA, MAML3, JADE2, MLLT10, and RERG, were not previously reported. Several new genes are known to be associated with traits genetically correlated with BP or to be involved in pathways associated with BP.Conclusion:Using new powerful methods of association analysis, we identified 7 novel genes associated with BP. Our results provide new insights into the genetics of back pain.

BACKGROUND CONTEXT:Previous studies have described utilization trends for lumbar facet pain procedures (LFP) over the past 2 decades in Medicare and commercially-insured populations. No studies have examined LFP utilization in the United States Veterans Health Administration (VHA) healthcare system. PURPOSE:To describe trends in utilization of LFP provided through VHA benefits from 2007-2020, including differences in utilization between VHA care and VHA-purchased care. STUDY DESIGN/SETTING:Retrospective cohort study. PATIENT SAMPLE:All Veterans in the VHA healthcare system. OUTCOME MEASURES:Annual rates of utilization of lumbar facet injections (LFI) and lumbar medial branch radiofrequency ablation (LMBRFA) procedures. METHODS:We used the VHA Corporate Data Warehouse to identify procedures to treat lumbar zygapophyseal joint pain performed in or purchased by VHA from 2007 to 2020. Descriptive analyses were performed to describe differences in utilization of LFI and LMBRFA procedures over time. RESULTS:During the 14-year study period, the number of LFP performed in or purchased by VHA per 100,000 enrollees increased by 298% for LFI and 767% for LMBRFA. The enrollee-adjusted growth in utilization for purchased care (1,586% [average annual growth of 122%] for LFI and 3,443% [average annual growth of 265%] for LMBRFA) outpaced observed growth in VHA care (70% [average annual growth of 5%] for LFI and 244% [average annual growth of 19%] for LMBRFA). Purchased care billed for more spinal levels during LFI than VHA care (5.32 vs 3.71) and performed more procedures than VHA facilities at the end of the study period (2020). CONCLUSION:There was substantial growth in the use of LFP among VHA enrollees from 2007-2020. Between 2007 and 2016, growth was greater than that in the Medicare and commercially-insured populations over the same time period. Growth was considerably greater among enrollees receiving LFP purchased by VHA from nonVHA facilities compared to VHA facilities. The steepest increase in utilization occurred after 2014, coinciding with policy changes to increase access to care provided by nonVHA providers.

Chronic back pain (CBP) is a disabling condition with a lifetime prevalence of 40% and a substantial socioeconomic burden. Because of the high heterogeneity of CBP, subphenotyping may help to improve prediction and support personalized treatment of CBP. To investigate CBP subphenotypes, we decomposed its genetic background into a shared one common to other chronic pain conditions (back, neck, hip, knee, stomach, and head pain) and unshared genetic background specific to CBP. We identified and replicated 18 genes with shared impact across different chronic pain conditions and two genes that were specific for CBP. Among people with CBP, we demonstrated that polygenic risk scores accounting for the shared and unshared genetic backgrounds of CBP may underpin different CBP subphenotypes. These subphenotypes are characterized by varying genetic predisposition to diverse medical conditions and interventions such as diabetes mellitus, myocardial infarction, diagnostic endoscopic procedures, and surgery involving muscles, bones, and joints.

Background:The purpose of this study is to examine whether chronic prescription opioid use in individuals with MS is associated with adverse medical outcomes and acute medical service utilization. Methods:This propensity score-matched, retrospective, cohort study included data from 15,377 Veterans with MS obtained from national VA administrative data. Veterans with filled prescriptions for chronic opioid therapy (n=1,908) in 2017 were matched 1:1 and compared to those not prescribed chronic opioid therapy using logistic regression models adjusted for propensity score, age, sex, race, and ethnicity. Outcomes included falls, fractures, wounds, and all-cause mortality, as well as acute inpatient and emergency department utilization, and intensive care unit admission in 2018. Results:The chronic opioid group had a higher likelihood of a fall (ORadj =1.77, 95% CI, 1.03-3.02, p=0.038), inpatient admission (ORadj=1.21, 95% CI, 1.02-1.43, p=0.028), and emergency department visit (ORadj=1.25, 95% CI, 1.09-1.43, p=0.001). Significant differences were not detected between those prescribed and not prescribed chronic opioid therapy on fractures, wounds, all-cause mortality, and intensive care unit admission, although in all cases the occurrence of these outcomes was higher in the opioid group. Conclusion:Chronic prescription opioid use among Veterans with MS was associated with a higher likelihood of adverse outcome (falls) and higher intensity health care utilization (inpatient admissions and emergency department visits) in the following year. Education regarding MS-specific risks of opioid use should be provided at initial prescription and re-evaluation of risks versus benefits should be conducted regularly.

Lumbar spinal stenosis (LSS) can be disabling and is a leading reason for spinal surgery in older adults. While nonsurgical treatments are recommended as first-line treatment, it remains unclear which patients will benefit most. To identify patient characteristics associated with larger improvements or larger treatment effects among adults receiving nonsurgical LSS interventions. Secondary analysis of a randomized controlled trial. Outpatient research clinics. 216 older adults with symptomatic LSS. Participants, recruited from November 2013 to June 2016, were randomized to receive: (1) manual therapy with an individualized exercise program (MTE); (2) a group exercise (GE) program; or (3) medical care (MC). We evaluated the association of baseline characteristics with 2-month change in primary outcomes: symptoms and function on the Swiss Spinal Stenosis questionnaire (SSSQ); and walking capacity in meters (m) on the self-paced walking test (SPWT). Baseline characteristics included sociodemographic and clinical variables. To explore heterogeneity of treatment effects, we evaluated unadjusted stratified estimates when comparing MTE to GE/MC. Additionally, we included an interaction term in models to test for statistical interaction. At baseline, participants (mean age = 72, 54

IMPORTANCE:The modest effect sizes of most pain treatments make it essential that randomized controlled trials (RCTs) use methods that clearly define treatment effects of interest and consider the role of concurrent treatments. OBJECTIVE:This study aims to determine how frequently concurrent analgesic use is reported in interventional pain RCTs and how accounting for analgesic use can affect estimates of pain intensity outcomes. DESIGN:Meta-epidemiologic study. METHODS:We conducted a study of concurrent analgesic use among RCTs from a recent systematic review of non-surgical interventional pain treatments (n = 37). We calculated the prevalence of methods used to report concurrent analgesic use. We performed meta-analyses to compare treatment effects on pain intensity with vs without accounting for concurrent analgesic use via a novel quantitative composite outcome, the "QPAC1.5." RESULTS:About half of interventional pain RCTs reported concurrent analgesic use, but only one directly accounted for concurrent analgesic use in their pain intensity outcome. Analyses accounting for concurrent analgesics using the QPAC1.5 substantially increased the estimated treatment effect of interventions on pain intensity by an average of -0.45 numeric rating scale points (95% CI -0.76 to -0.14; P < 0.001), as compared to analyses that did not adjust for analgesic use. CONCLUSIONS AND RELEVANCE:Concurrent analgesic use is sometimes reported in interventional pain RCTs, but rarely accounted for when examining treatment effects on pain intensity. Accounting for concurrent analgesic use may mitigate the effects of that use and substantially impact estimated treatment effect sizes.

Objective: We conducted a Mendelian randomization (MR) study to examine causal associations of C-reactive protein (CRP) with (1) spinal pain; (2) extent of multisite chronic pain; and (3) chronic widespread musculoskeletal pain. Design: Two-sample MR study. Setting/Subjects: We used summary statistics from publicly available genome-wide association studies (GWAS) conducted in multiple cohorts and biobanks. Genetic instrumental variables were taken from an exposure GWAS of CRP (n=204,402). Outcome GWASs examined spinal pain (n=1,028,947), extent of multisite chronic pain defined as the number of locations with chronic pain (n=387,649), and chronic widespread pain (n=249,843). Methods: We examined MR evidence for causal associations using inverse-variance weighted (IVW) analysis and sensitivity analyses using other methods. We calculated odds ratios (ORs), 95% confidence intervals (95% CIs), and p-values, using a Bonferroni correction (p<0.0166) to account for 3 primary comparisons. Results: Greater serum CRP (mg/L) was not significantly causally associated with spinal pain (OR=1.04, 95% CI 1.00-1.08; p=0.07) in IVW analysis. Greater serum CRP also showed no significant causal association with extent of multisite chronic pain in IVW analysis (beta coefficient= 0.014, standard error=0.011; p=0.19). CRP also showed no significant causal association with chronic widespread pain in IVW analysis (OR=1.00, 95% CI 1.00-1.00; p=0.75). All secondary and sensitivity analyses also showed no significant associations. Conclusions: This MR study found no causal association of CRP on spinal pain, the extent of chronic pain, or chronic widespread pain. Future studies examining mechanistic biomarkers for pain conditions should consider other candidates besides CRP.

Analytical methods to incorporate potential concurrent analgesic use into primary statistical summaries are underutilized in pain randomized controlled trials (RCTs). Without valid inclusion of analgesic use, the primary analyses of pain may produce diminished estimated treatment effects. We used contemporary causal inference methods that can account for concurrent treatment to reanalyze RCT data examining the effect of epidural steroid injection (ESI). Specifically, we define an "attributable to ESI estimand", which is the controlled direct effect of ESI. We used a simple composite pain intensity outcome, the QPAC1.5, and structural mean models (SMM) to estimate the target estimand. Compared to traditional methods such as strict intention to treat analysis (strict ITT) , SMMs can account for analgesic use without assuming sequential ignorability. We estimated treatment effects of ESI on leg pain intensity (LPI) using the numeric rating scale (NRS) with strict ITT, 3 SMM estimating methods (estimating equations [EE], g-estimation, and generalized method of moments [GMM]), and the QPAC1.5. The treatment effect of ESI on LPI using strict ITT was -0.751 NRS points (95% confidence interval [CI]: [-1.287, -0.214]). Estimates for the attributable to ESI estimand were -0.864 (95% CI: [-3.207, 1.478]) for EE, -0.935 (95% CI: [-1.779, 0.090]) for g-estimation, -0.653 (95% CI: [-1.218, -0.089]]) for GMM, and -0.930 (95% CI: [-1.508, -0.352]) for the QPAC1.5. We illustrate how contemporary causal inference methods and alternative estimands can be used to account for concurrent analgesic use in pain RCTs, in a manner that may result in larger treatment effects.

Importance Physical activity is considered to have both detrimental and beneficial effects on low back pain (LBP). Objectives To examine the association of transient (short-term) risk of 10 common physical activities with participant-reported LBP exacerbations (flares) and to estimate cumulative (long-term) risks of each activity with LBP-related functional limitations at 1-year follow-up. Design, Setting, and Participants This prospective, longitudinal case-crossover study nested in a cohort study recruited adults with recent health care visits for LBP at outpatient clinics in Veterans Affairs primary care from March 25, 2021, to September 21, 2023. Participants were followed up for 1 year. Exposures The number of hours engaged in each activity in the past 24 hours. Main Outcomes and Measures Presence of a participant-reported LBP flare (aim 1) and LBP-related functional limitations at 1-year follow-up (aim 2). Results A total of 416 participants (mean [SD] age, 47.5 [10.9] years; 306 [75%] male) completed 9757 surveys during the 1-year follow-up. Each additional hour in which an activity was performed at least once in that hour was associated with greater risk of subsequent flares for lifting more than 10 lb (odds ratio per hour, 1.05; 95% CI, 1.03-1.07), bending, pushing/pulling, twisting, and squatting. Total duration of sitting was associated with lower risk of flares (odds ratio per additional hour sitting, 0.96; 95% CI, 0.94-0.98). However, the mean hours spent in each activity during the initial 8 weeks of the study was not associated with long-term functional limitations at 1-year follow-up. Conclusions and Relevance This study found short-term, transient risks of LBP flares associated with some activities but no associations with functional limitations at 1-year follow-up. These findings suggest that people with LBP who engage in more of these activities do not have better or worse long-term outcomes.