---
title: "SPOT: Early prediction of 12-month pain trajectories after intra-articular knee injections"
id: "pubmed-42671292"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42671292"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42671292/"
doi: "10.1002/jor.70270"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# SPOT: Early prediction of 12-month pain trajectories after intra-articular knee injections
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42671292
- **Specialty:** [General](https://medichelpline.com/clinical-feed/general.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42671292/)
- **DOI:** [10.1002/jor.70270](https://doi.org/10.1002%2Fjor.70270)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This randomized, multisite trial analyzed patient-reported pain to model 12-month postinjection pain trajectories in knee osteoarthritis (KOA) patients treated with orthobiologic intra-articular injections. - Data came from participants randomized to autologous bone marrow aspirate concentrate, umbilical cord tissue-derived mesenchymal stromal cells, or stromal vascular fraction within a larger single-blind trial. - After data-quality screening, the trajectory analysis cohort included **317** participants; the prediction cohort (with Screening and Month-3 KOOS-12 Pain scores) included **295** participants. - Latent class mixed-effects modeling favored a two-class, clinically interpretable solution: **66.6%** of patients followed an **Improved Pain** trajectory and **33.4%** followed a **Persistent Pain** trajectory. A three-class model had a slightly lower BIC but added a very small class (2.5%) and was not used for the prediction tool. - A logistic regression prediction model used **KOOS-12 Pain** at Screening and 3-month change to predict trajectory membership. - Model performance: training AUC = **0.785**; held-out test AUC = **0.792**. Using a training-selected threshold of **0.656**, the held-out test set showed sensitivity = **0.790**, specificity = **0.692**, PPV = **0.860**, NPV = **0.581**, and accuracy = **0.761**. - The prediction algorithm was implemented as the web-based Symptom Prediction for Outcomes of Treatment (**SPOT**) calculator; it requires only Screening and Month-3 KOOS-12 Pain data to classify likely trajectory (Improved vs. Persistent). - Clinical significance presented: SPOT enables early classification of likely 12-month pain trajectories after orthobiologic KOA treatment using routine patient-reported outcome measures. - Trial registration: ClinicalTrials.gov identifier **NCT03818737**. - Keywords reported include **KOOS-12**, knee osteoarthritis, latent class mixed-effects modeling, patient-reported outcomes, and prediction model.
## Clinical Analysis & Structured Key Points
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Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, Georgia, USA."), [Hicham Drissi](https://pubmed.ncbi.nlm.nih.gov/?term=Drissi+H&cauthor_id=42671292)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#full-view-affiliation-3 "Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#full-view-affiliation-5 "Department of Veterans Affairs, Atlanta VA Medical Center, Decatur, Georgia, USA."), [Jed A Diekfuss](https://pubmed.ncbi.nlm.nih.gov/?term=Diekfuss+JA&cauthor_id=42671292)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#full-view-affiliation-1 "Emory Sports Performance And Research Center \(SPARC\), Flowery Branch, Georgia, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#full-view-affiliation-2 "Emory Human Performance Institute, Atlanta, Georgia, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#full-view-affiliation-3 "Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#full-view-affiliation-5 "Department of Veterans Affairs, Atlanta VA Medical Center, Decatur, Georgia, USA.") Affiliations Expand ### Affiliations * 1 Emory Sports Performance And Research Center (SPARC), Flowery Branch, Georgia, USA. * 2 Emory Human Performance Institute, Atlanta, Georgia, USA. * 3 Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA. * 4 Center for Medical Ethics and Health Policy Baylor College of Medicine, Houston, Texas, USA. * 5 Department of Veterans Affairs, Atlanta VA Medical Center, Decatur, Georgia, USA. * 6 Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, Georgia, USA. * PMID: **42671292** * DOI: [ 10.1002/jor.70270 ](https://doi.org/10.1002/jor.70270) Item in Clipboard Randomized Controlled Trial # SPOT: An Early Detection Tool for Predicting Pain Trajectories Following Intra-Articular Injections Brittany L Nelson et al. J Orthop Res. 2026 Sep. Show details Display options Display options Format Abstract PubMed PMID J Orthop Res Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22J+Orthop+Res%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22J+Orthop+Res%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671292/) . 2026 Sep;44(9):e70270. doi: 10.1002/jor.70270. ### Authors [Brittany L Nelson](https://pubmed.ncbi.nlm.nih.gov/?term=Nelson+BL&cauthor_id=42671292)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-1 "Emory Sports Performance And Research Center \(SPARC\), Flowery Branch, Georgia, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-2 "Emory Human Performance Institute, Atlanta, Georgia, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-3 "Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-4 "Center for Medical Ethics and Health Policy Baylor College of Medicine, Houston, Texas, USA."), [Prathap Jayaram](https://pubmed.ncbi.nlm.nih.gov/?term=Jayaram+P&cauthor_id=42671292)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-3 "Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA."), [Scott D Boden](https://pubmed.ncbi.nlm.nih.gov/?term=Boden+SD&cauthor_id=42671292)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-3 "Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA."), [Kenneth Mautner](https://pubmed.ncbi.nlm.nih.gov/?term=Mautner+K&cauthor_id=42671292)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-3 "Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA."), [Michael B Gottschalk](https://pubmed.ncbi.nlm.nih.gov/?term=Gottschalk+MB&cauthor_id=42671292)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-3 "Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA."), [Gregory D Myer](https://pubmed.ncbi.nlm.nih.gov/?term=Myer+GD&cauthor_id=42671292)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-1 "Emory Sports Performance And Research Center \(SPARC\), Flowery Branch, Georgia, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-2 "Emory Human Performance Institute, Atlanta, Georgia, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-3 "Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-5 "Department of Veterans Affairs, Atlanta VA Medical Center, Decatur, Georgia, USA.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-6 "Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, Georgia, USA."), [Hicham Drissi](https://pubmed.ncbi.nlm.nih.gov/?term=Drissi+H&cauthor_id=42671292)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-3 "Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-5 "Department of Veterans Affairs, Atlanta VA Medical Center, Decatur, Georgia, USA."), [Jed A Diekfuss](https://pubmed.ncbi.nlm.nih.gov/?term=Diekfuss+JA&cauthor_id=42671292)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-1 "Emory Sports Performance And Research Center \(SPARC\), Flowery Branch, Georgia, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-2 "Emory Human Performance Institute, Atlanta, Georgia, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-3 "Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42671292/#short-view-affiliation-5 "Department of Veterans Affairs, Atlanta VA Medical Center, Decatur, Georgia, USA.") ### Affiliations * 1 Emory Sports Performance And Research Center (SPARC), Flowery Branch, Georgia, USA. * 2 Emory Human Performance Institute, Atlanta, Georgia, USA. * 3 Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA. * 4 Center for Medical Ethics and Health Policy Baylor College of Medicine, Houston, Texas, USA. * 5 Department of Veterans Affairs, Atlanta VA Medical Center, Decatur, Georgia, USA. * 6 Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, Georgia, USA. * PMID: **42671292** * DOI: [ 10.1002/jor.70270 ](https://doi.org/10.1002/jor.70270) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract The purpose of this study was to identify 12-month postinjection knee osteoarthritis (KOA) pain trajectories and develop an early prediction model using patient-reported pain scores. Data were derived from a multi-site, single-blind randomized controlled trial of intra-articular injections for KOA. The primary analysis focused on participants assigned to autologous bone marrow aspirate concentrate, umbilical cord tissue-derived mesenchymal stromal cells, or stromal vascular fraction. After data-quality screening, the primary trajectory cohort included 317 participants and the prediction cohort included 295 participants with Screening and Month-3 KOOS-12 Pain scores. Latent class mixed-effects modeling identified a two-class solution selected for clinical interpretability: 66.6% of patients followed an Improved Pain trajectory and 33.4% followed a Persistent Pain trajectory. Although a three-class model had slightly lower BIC, the additional class included only 2.5% of participants and was not retained for the clinical prediction tool. A logistic regression model using KOOS-12 Pain at Screening and 3-month change predicted trajectory membership with AUC = 0.785 in training and AUC = 0.792 in the held-out test set. A training-selected threshold of 0.656 yielded held-out test sensitivity = 0.790, specificity = 0.692, PPV = 0.860, NPV = 0.581, and accuracy = 0.761. The resultant model was implemented as the Symptom Prediction for Outcomes of Treatment (SPOT) web calculator. Clinical Significance: The SPOT web calculator only requires KOOS-12 Pain data from Screening and Month 3 to classify patients as likely to follow an Improved Pain vs. Persistent Pain trajectory after orthobiologic KOA treatment. Trial Registration: ClinicalTrials.gov identifier: [NCT03818737](http://clinicaltrials.gov/show/NCT03818737 "See in ClinicalTrials.gov"). **Keywords:** 12‐item knee injury and osteoarthritis outcome score; knee osteoarthritis; latent class mixed‐effects modeling; patient‐reported outcomes; prediction model. © 2026 Orthopaedic Research Society. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## References 1. 1. L. Sharma, “Osteoarthritis of the Knee,” New England Journal of Medicine 384, no. 1 (2021): 51–59. 2. 1. A. V. Bedenbaugh, M. Bonafede, E. H. Marchlewicz, V. Lee, and J. Tambiah, “Real‐World Health Care Resource Utilization and Costs Among US Patients With Knee Osteoarthritis Compared With Controls,” ClinicoEconomics and Outcomes Research 13 (2021): 421–435. 3. 1. A. Boada‐Pladellorens, M. Avellanet, E. Pages‐Bolibar, and A. Veiga, “Stromal Vascular Fraction Therapy for Knee Osteoarthritis: A Systematic Review,” Therapeutic Advances in Musculoskeletal Disease 14 (2022): 1759720X221117879. 4. 1. I. K. Bolia, S. Bougioukli, W. J. Hill, et al., “Clinical Efficacy of Bone Marrow Aspirate Concentrate Versus Stromal Vascular Fraction Injection in Patients With Knee Osteoarthritis: A Systematic Review and Meta‐Analysis,” American Journal of Sports Medicine 50, no. 5 (2022): 1451–1461. 5. 1. J. Matas, M. Orrego, D. Amenabar, et al., “Umbilical Cord‐Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial,” Stem Cells Translational Medicine 8, no. 3 (2019): 215–224. Show all 33 references ## Publication types * Randomized Controlled Trial Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Randomized+Controlled+Trial%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Randomized+Controlled+Trial) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671292/) * Multicenter Study Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Multicenter+Study%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Multicenter+Study) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671292/) ## MeSH terms * Aged Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.
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