Advantages to interspace-level analyses over person-level analyses when studying relationships between lumbar spinal degeneration findings : a cross-sectional study.

Purpose: 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), and (3) a conventional person-level analytic approach.

Methods: Adults in primary care (n=147) received lumbar spine magnetic resonance imaging (MRI) and neuroradiologist-evaluated assessments of prevalent disc height narrowing (DHN), type II MC, and other LDD parameters.

Use of Biologic or Targeted Synthetic Disease-Modifying Antirheumatic Drugs and Cancer Risk.

Importance: The Oral Rheumatoid Arthritis Trial Surveillance demonstrated an increased cancer risk among patients with rheumatoid arthritis (RA) taking tofacitinib compared with those taking tumor necrosis factor inhibitors (TNFis). Although international cohort studies have compared cancer outcomes between TNFis, non-TNFi drugs, and Janus kinase inhibitor (JAKis), their generalizability to US patients with RA is limited.

Objective: To assess the comparative safety of TNFis, non-TNFi drugs, and JAKis among US patients with RA (ie, the cancer risk associated with the use of these drugs among these patients).

Impact of electronic health record updates and changes on the delivery and monitoring of interventions in embedded pragmatic clinical trials.

The NIH Pragmatic Trials Collaboratory supports the design and conduct of 32 embedded pragmatic clinical trials, and many of these trials rely on data from the electronic health record (EHR) to monitor outcomes and/or use functionality provided by the EHR platform to deliver the intervention. Given the complexity and dynamic nature of EHR systems, study teams have encountered challenges in use of the EHR for these purposes, including challenges related to local implementation of trial interventions, rapid technology evolution, EHR updates, and transitions in EHR systems. In this article, we share case examples and lessons learned, and suggest that teams need to be aware of-and perhaps proactively investigate- possible changes to EHR systems and data that will affect the delivery of interventions and the integrity and safety of pragmatic clinical trials.

Adverse respiratory events during treatment with gabapentin and opioids among older adults with spine-related conditions: a propensity-matched cohort study in the US Medicare population.

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 spine-related diagnoses treated with gabapentin + opioids vs those treated with tricyclic antidepressants (TCA) or duloxetine + opioids.

Subject-level spinal osteoporotic fracture prediction combining deep learning vertebral outputs and limited demographic data.

Unlabelled: Automated screening for vertebral fractures could improve outcomes. We achieved an AUC-ROC = 0.968 for the prediction of moderate to severe fracture using a GAM with age and three maximal vertebral body scores of fracture from a convolutional neural network.

Mortality with concurrent treatment with gabapentin and opioids among people with spine diagnoses in the U.S. Medicare population: a propensity-matched cohort study.

Importance: Given the negative impact of opioid use on population health, prescriptions for alternative pain-relieving medications, including gabapentin, have increased. Concurrent gabapentin and opioid prescriptions are commonly reported in retrospective studies of opioid-related overdose deaths.

Objective: To determine whether people who filled gabapentin and opioid prescriptions concurrently ('gabapentin + opioids') had greater mortality than those who filled an active control medication (tricyclic antidepressants [TCAs] or duloxetine) and opioids concurrently ('TCAs/duloxetine + opioids').

Cost-Effectiveness of Artificial Intelligence-Based Opportunistic Compression Fracture Screening of Existing Radiographs.

Purpose: Osteoporotic vertebral compression fractures (OVCFs) are a highly prevalent source of morbidity and mortality, and preventive treatment has been demonstrated to be both effective and cost effective. To take advantage of the information available on existing chest and abdominal radiographs, the authors' study group has developed software to access these radiographs for OVCFs with high sensitivity and specificity using an established artificial intelligence deep learning algorithm. The aim of this analysis was to assess the potential cost-effectiveness of implementing this software.

Factors Affecting Post-trial Sustainment or De-implementation of Study Interventions: A Narrative Review.

In contrast to traditional randomized controlled trials, embedded pragmatic clinical trials (ePCTs) are conducted within healthcare settings with real-world patient populations. ePCTs are intentionally designed to align with health system priorities leveraging existing healthcare system infrastructure and resources to ease intervention implementation and increase the likelihood that effective interventions translate into routine practice following the trial. The NIH Pragmatic Trials Collaboratory, funded by the National Institutes of Health (NIH), supports the conduct of large-scale ePCT Demonstration Projects that address major public health issues within healthcare systems.

Frailty and Risk of Serious Infections in Patients With Rheumatoid Arthritis Treated With Biologic or Targeted-Synthetic Disease-Modifying Antirheumatic Drugs.

Objective: It remains unknown whether frailty status portends an increased risk of adverse outcomes in patients with rheumatoid arthritis (RA) initiating biologic or targeted-synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The objective of our study was to evaluate the association between frailty and serious infections in a younger population of patients (<65 years old) with RA who initiated b/tsDMARDs.

Methods: Using MarketScan data, we identified new users of tumor necrosis factor inhibitors (TNFi), non-TNFi biologic DMARDs, or Janus kinase inhibitors (JAKi) between 2008 and 2019 among those with RA.

Red flags to screen for vertebral fracture in people presenting with low back pain.

Background: Low back pain is a common presentation across different healthcare settings. Clinicians need to confidently be able to screen and identify people presenting with low back pain with a high suspicion of serious or specific pathology (e.g.

Generalizability of Deep Learning Classification of Spinal Osteoporotic Compression Fractures on Radiographs Using an Adaptation of the Modified-2 Algorithm-Based Qualitative Criteria.

Rationale And Objectives: Spinal osteoporotic compression fractures (OCFs) can be an early biomarker for osteoporosis but are often subtle, incidental, and underreported. To ensure early diagnosis and treatment of osteoporosis, we aimed to build a deep learning vertebral body classifier for OCFs as a critical component of our future automated opportunistic screening tool.

Materials And Methods: We retrospectively assembled a local dataset, including 1790 subjects and 15,050 vertebral bodies (thoracic and lumbar).

Mortality among older adults with osteoporotic vertebral fracture.

Unlabelled: We evaluated whether older adults who received kyphoplasty had reduced risk of mortality compared to those who did not. In unmatched analyses, those receiving kyphoplasty were at reduced risk of death but after matching on age and medical complications, patients who received kyphoplasty were at increased risk of death.

Purpose: In previous observational studies, kyphoplasty for treatment of osteoporotic vertebral fractures has been associated with decreased mortality compared to conservative management.

Treatment With Opioids Is Not Associated With Poor Outcomes Among Older Adults With Lumbar Spinal Stenosis Receiving Epidural Injections.

Study Design: Secondary analysis of a randomized controlled trial.

Objective: To assess how baseline treatment with opioids is associated with pain and function in older adults with lumbar spinal stenosis who receive epidural injections.

Summary Of Background Data: Data were obtained from the Lumbar Epidural Steroid injections for Spinal Stenosis trial, a double-blind, multisite, randomized controlled trial.

Intervention delivery for embedded pragmatic clinical trials: Development of a tool to measure complexity.

Background: Conducting an embedded pragmatic clinical trial in the workflow of a healthcare system is a complex endeavor. The complexity of the intervention delivery can have implications for study planning, ability to maintain fidelity to the intervention during the trial, and/or ability to detect meaningful differences in outcomes.

Methods: We conducted a literature review, developed a tool, and conducted two rounds of phone calls with NIH Pragmatic Trials Collaboratory Demonstration Project principal investigators to develop the Intervention Delivery Complexity Tool.

Predicting decompression surgery by applying multimodal deep learning to patients' structured and unstructured health data.

Background: Low back pain (LBP) is a common condition made up of a variety of anatomic and clinical subtypes. Lumbar disc herniation (LDH) and lumbar spinal stenosis (LSS) are two subtypes highly associated with LBP. Patients with LDH/LSS are often started with non-surgical treatments and if those are not effective then go on to have decompression surgery.

m2ABQ-a proposed refinement of the modified algorithm-based qualitative classification of osteoporotic vertebral fractures.

Unlabelled: Currently, there is no reproducible, widely accepted gold standard to classify osteoporotic vertebral body fractures (OVFs). The purpose of this study is to refine a method with clear rules to classify OVFs for machine learning purposes. The method was found to have moderate interobserver agreement that improved with training.

Improving Power and Accuracy in Randomized Controlled Trials of Pain Treatments by Accounting for Concurrent Analgesic Use.

The 0 to 10 numeric rating scale of pain intensity is a standard outcome in randomized controlled trials (RCTs) of pain treatments. For individuals taking analgesics, there may be a disparity between "observed" pain intensity (pain intensity with concurrent analgesic use) and pain intensity without concurrent analgesic use (what the numeric rating scale would be had analgesics not been taken). Using a contemporary causal inference framework, we compare analytic methods that can potentially account for concurrent analgesic use, first in statistical simulations, and second in analyses of real (non-simulated) data from an RCT of lumbar epidural steroid injections.

Estimating individualized treatment effects using a risk-modeling approach: an application to epidural steroid injections for lumbar spinal stenosis.

Conventional "1-variable-at-a-time" analyses to identify treatment effect modifiers are often underpowered and prone to false-positive results. This study used a "risk-modeling" approach guided by the Predictive Approaches to Treatment effect Heterogeneity (PATH) Statement framework: (1) developing and validating a multivariable model to estimate predicted future back-related functional limitations as measured by the Roland-Morris Disability Questionnaire (RMDQ) and (2) stratifying patients from a randomized controlled trial (RCT) of lumbar epidural steroid injections (LESIs) for the treatment of lumbar spinal stenosis into subgroups with different individualized treatment effects on RMDQ scores at the 3-week follow-up. Model development and validation were conducted in a cohort (n = 3259) randomly split into training and testing sets in a 4:1 ratio.

The Lumbar Stenosis Prognostic Subgroups for Personalizing Care and Treatment (PROSPECTS) study: protocol for an inception cohort study.

Background: Lumbar spinal stenosis (LSS) is a common degenerative condition that contributes to back and back-related leg pain in older adults. Most patients with symptomatic LSS initially receive non-operative care before surgical consultation. However, there is a scarcity of data regarding prognosis for patients seeking non-surgical care.

Osteoporosis identification among previously undiagnosed individuals with vertebral fractures.

Unlabelled: Because osteoporosis is under-recognized in patients with vertebral fractures, we evaluated characteristics associated with osteoporosis identification. Most patients with vertebral fractures did not receive evaluation or treatment for osteoporosis. Black, younger, and male participants were particularly unlikely to have had recognized osteoporosis, which could increase their risk of negative outcomes.

Long-term effectiveness of epidural steroid injections after new episodes of low back pain in older adults.

Background: There is limited research on the long-term effectiveness of epidural steroid injections (ESI) in older adults despite the high prevalence of back and leg pain in this age group. We tested the hypotheses that older adults undergoing ESI, compared to patients not receiving ESI: (1) have worse pain, disability and quality of life ('outcomes') pre-ESI, (2) have improved outcomes after ESI and (3) have improved outcomes due to a specific ESI effect.

Methods: We prospectively studied patients ≥65 years old presenting to primary care with new episodes of back pain in three US healthcare systems (BOLD registry).