A Computational Strategy for the Rapid Identification and Ranking of Patient-Specific T cell Receptors Bound to Neoantigens.

T Cell Receptor (TCR) recognition of a peptide-major histocompatibility complex (pMHC) is crucial for adaptive immune response. The identification of therapeutically relevant TCR-pMHC protein pairs is a bottleneck in the implementation of TCR-based immunotherapies. The ability to computationally design TCRs to target a specific pMHC requires automated integration of next-generation sequencing, protein-protein structure prediction, molecular dynamics, and TCR ranking. We present a pipeline to evaluate patient-specific, sequence-based TCRs to a target pMHC. Using the three most frequently expressed TCRs from 16 colorectal cancer patients, we predict the protein-protein structure of the TCRs to the target CEA peptide-MHC using Modeller and ColabFold. TCR-pMHC structures are compared using automated equilibration and successive analysis. ColabFold generated configurations require a ∼2.5X reduction in equilibration time of TCR-pMHC structures compared to Modeller. The structural differences between Modeller and ColabFold are demonstrated by root mean square deviation (∼0.20 nm) between clusters of equilibrated configurations, which impact the number of hydrogen bonds and Lennard-Jones contacts between the TCR and pMHC. We identify TCR ranking criteria that may prioritize TCRs for evaluation of in vitro immunogenicity and validate this ranking by comparing to state-of-the-art machine learning based methods trained to predict the probability of TCR-pMHC binding. This article is protected by copyright. All rights reserved.

Telehealth delivery of physical therapist-led interventions for persons with chronic low back pain in underserved communities: lessons from pragmatic clinical trials.

In this perspective, we present our experience developing and conducting two pragmatic clinical trials investigating physical therapist-led telehealth strategies for persons with chronic low back pain. Both trials, the BeatPain Utah and AIM-Back trials, are part of pragmatic clinical trial collaboratories and are being conducted with persons from communities that experience pain management disparities. Practice guidelines recommend nonpharmacologic care, and advise against opioid therapy, for the primary care management of persons with chronic low back pain. Gaps between these recommendations and actual practice patterns are pervasive, particularly for persons from racial or ethnic minoritized communities, those with fewer economic resources, and those living in rural areas including Veterans. Access barriers to evidence-based nonpharmacologic care, which is often provided by physical therapists, have contributed to these evidence-practice gaps. Telehealth delivery has created new opportunities to overcome access barriers for nonpharmacologic pain care. As a relatively new delivery mode however, telehealth delivery of physical therapy comes with additional challenges related to technology, intervention adaptations and cultural competence. The purpose of this article is to describe the challenges encountered when implementing telehealth physical therapy programs for persons with chronic low back pain in historically underserved communities. We also discuss strategies developed to overcome barriers in an effort to improve access to telehealth physical therapy and reduce pain management disparities. Inclusion of diverse and under-represented communities in pragmatic clinical trials is a critical consideration for improving disparities, but the unique circumstances present in these communities must be considered when developing implementation strategies.

Vascular dysfunction in hemorrhagic viral fevers: opportunities for organotypic modeling.

The hemorrhagic fever viruses (HFVs) cause severe or fatal infections in humans. Named after their common symptom hemorrhage, these viruses induce significant vascular dysfunction by affecting endothelial cells, altering immunity, and disrupting the clotting system. Despite advances in treatments, such as cytokine blocking therapies, disease modifying treatment for this class of pathogen remains elusive. Improved understanding of the pathogenesis of these infections could provide new avenues to treatment. While animal models and traditional 2D cell cultures have contributed insight into the mechanisms by which these pathogens affect the vasculature, these models fall short in replicatingin vivohuman vascular dynamics. The emergence of microphysiological systems (MPSs) offers promising avenues for modeling these complex interactions. These MPS or 'organ-on-chip' models present opportunities to better mimic human vascular responses and thus aid in treatment development. In this review, we explore the impact of HFV on the vasculature by causing endothelial dysfunction, blood clotting irregularities, and immune dysregulation. We highlight how existing MPS have elucidated features of HFV pathogenesis as well as discuss existing knowledge gaps and the challenges in modeling these interactions using MPS. Understanding the intricate mechanisms of vascular dysfunction caused by HFV is crucial in developing therapies not only for these infections, but also for other vasculotropic conditions like sepsis.

Transition from Acute to Chronic Low Back Pain in a Community-Based Cohort.

The transition from acute to chronic low back pain (LBP) in community settings has yet to be well understood. We recruited n=131 participants with acute LBP from the community and followed them for 3 and 6-month outcomes. Acute LBP was defined by a duration of < 4 weeks, and participants must have reported a 30-day LBP-free period before the current acute episode. Chronic LBP was defined as pain most or every day over the past 3 months. Baseline psychological, social, and demographic factors were examined as predictors of transition to chronic LBP at 3 months or continuation of chronic LBP at 6 months. The transition from acute to chronic LBP at 3 months was 32.2% ( 38/118). At 6 months, 80.7% (25/111) of participants who transitioned at 3 months continued to have chronic LBP. At 6 months, participants who identified as Black or African American were more likely than white participants to transition to chronic LBP (RR=1.76, 95% CI 1.05, 2.95) and more likely to continue to have chronic LBP (RR=2.19, 95% CI 1.14, 4.21). Those classified at baseline by both LBP most or every day and intensity of at least 30/100 were more likely to transition to chronic LBP (RR=3.13, 95% CI 1.84, 5.30) and continue to have chronic LBP at 6 months (RR=2.58, 95% CI 1.43, 4.16). The STarT Back Screening Tool and the OSPRO-YF were associated with the transition to chronic LBP at 3 months and continuation at 6 months. Participants with higher PROMIS General Health and PROMIS Physical Health scores were less likely to transition to chronic LBP or continue to have chronic LBP at 6 months. These findings identify factors of acute LBP in the community that may predict the transition to chronic LBP. Larger studies are needed to confirm these findings and better understand the mechanisms driving the transition to chronic LBP.

Developing a Computer Vision Model to Automate Quantitative Measurement of Hip-Knee-Ankle Angle in Total Hip and Knee Arthroplasty Patients.

BACKGROUND: Increasing deformity of the lower extremities, as measured by the hip-knee-ankle angle (HKAA), is associated with poor patient outcomes after total hip and knee arthroplasty (THA, TKA). Automated calculation of HKAA is imperative to reduce the burden on orthopaedic surgeons. We proposed a detection-based deep learning (DL) model to calculate HKAA in THA and TKA patients and assessed the agreement between DL-derived HKAAs and manual measurement. METHODS: We retrospectively identified 1,379 long-leg radiographs (LLRs) from patients scheduled for THA or TKA within an academic medical center. There were 1,221 LLRs used to develop the model (randomly split into 70% training, 20% validation, and 10% held-out test sets); 158 LLRs were considered "difficult," as the femoral head was difficult to distinguish from surrounding tissue. There were 2 raters who annotated the HKAA of both lower extremities, and inter-rater reliability was calculated to compare the DL-derived HKAAs with manual measurement within the test set. RESULTS: The DL model achieved a mean average precision of 0.985 on the test set. The average HKAA of the operative leg was 173.05 ± 4.54°; the nonoperative leg was 175.55 ± 3.56°. The inter-rater reliability between manual and DL-derived HKAA measurements on the operative leg and nonoperative leg indicated excellent reliability (intraclass correlation (2,k) = 0.987 [0.96, 0.99], intraclass correlation (2, k) = 0.987 [0.98, 0.99, respectively]). The standard error of measurement for the DL-derived HKAA for the operative and nonoperative legs was 0.515° and 0.403°, respectively. CONCLUSIONS: A detection-based DL algorithm can calculate the HKAA in LLRs and is comparable to that calculated by manual measurement. The algorithm can detect the bilateral femoral head, knee, and ankle joints with high precision, even in patients where the femoral head is difficult to visualize.

Clinimetric Properties of the Working Alliance Inventory and Credibility Expectancy Questionnaire: Screening Options for Musculoskeletal Pain.

OBJECTIVE: To investigate clinimetric properties of 2 surveys used to evaluate common factors in the patient-provider relation and present screener options for the assessment of common factors and report their correlation with pain and functional outcomes. DESIGN: Observational cohort. SETTING: Outpatient physical therapy. PARTICIPANTS: 100 individuals (58% women, mean age=34, SD=15; N=100) presenting to physical therapy with musculoskeletal pain in the following regions: 44% lower extremity, 36% spine, 19% upper extremity, 1% undetermined. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Participants completed the Working Alliance Inventory (WAI) and the Credibility and Expectancy Questionnaire (CEQ). Exploratory factor analysis (EFA) explored factor structure of the WAI and CEQ. Internal consistency was evaluated for scales derived from items retained based on factor loadings. Finally, options for screener tools were proposed and assessed based on their correlation to original surveys as well as pain and functional outcomes. RESULTS: The data supported a 4-factor structure for the surveys. Some WAI items were excluded due to cross-loading. The derived four-factor scales demonstrated strong correlations with the original surveys (r=.89-.99) and exhibited good internal consistency (α=.824-.875). Two screening options were suggested: 1 retaining 11 of the original 18 items and the other comprising just 3 items. Both screening tools correlated with the original surveys and showed associations with improvements in pain and functional outcomes (r=-.21-.34). CONCLUSION: The proposed screeners provide concise measurement options to facilitate use in clinical practice. These tools can aid in facilitating patient communication specifically addressing patient expectation and understanding the tasks required to enact behavior change.

Utility of Patient Reported Outcome Measurement Information System measures in predicting shoulder arthroplasty in patients with shoulder osteoarthritis.

BACKGROUND: The decision to treat shoulder osteoarthritis (OA) definitively with shoulder arthroplasty (SA) is multifactorial, considering objective findings, subjective information, and patient goals. The first goal of this study was to determine if Patient Reported Outcome Measurement Information System (PROMIS) measures correlated with patients with shoulder OA who underwent SA within 1 year. The second goal of this study was to determine if score cut-offs in PROMIS domains could further discriminate which shoulder OA patients underwent SA within 1 year. METHODS: This retrospective case-control study examined patients with a diagnosis of shoulder OA who consulted an orthopedic provider from November 1, 2020 to May 23, 2022, and recorded PROMIS measures in the domains of Physical Function, Depression, and/or Pain Interference. A surgical group was defined as patients who underwent SA within 1 year of the most recent PROMIS measures and the nonsurgical patients were defined as the control group. Mean PROMIS scores were compared between the surgical and control groups. Separate logistic regression models controlling for age, race, ethnicity, and comorbidity count were performed for each PROMIS domain as a 1) continuous variable, and then as 2) binary variable defined by PROMIS score cut-off points to determine which scores correlated with undergoing SA to further characterize the potential clinical utility of PROMIS score cut-offs in relating to undergoing SA. RESULTS: The surgical group of 478 patients was older (68.2 vs. 63.8 years), more often of White race (82.6% vs. 70.9%), and less often of Hispanic Ethnicity (1.5% vs. 2.9%) than the control group of 3343 patients. Using optimal cut-offs in PROMIS scores, Pain Interference ≥63 (odds ratio [OR] = 2.97 (2.41-3.64), P < .001), Physical Function ≤39 (OR = 1.81 (95% confidence interval, 1.48-2.22), P < .001), and depression ≥49 (OR = 1.82 (95% confidence interval, 1.50-2.22), P < .001) were all found to correlate with undergoing SA within 1 year in multivariable logistic regressions. CONCLUSION: The results of this study demonstrate that cut-off scores for PROMIS measures differentiated patients undergoing SA within 1 year. These cut-off scores may have clinical utility in aiding in decision-making regarding surgical candidates for SA. Further research is needed to validate these cut-off scores and determine how they relate to patient outcomes after SA.

General and Pain-Associated Psychological Distress Phenotypes Among Patients With Low Back Pain in the Military Health System.

OBJECTIVE: The primary objective was to describe rates of general and pain-related psychological distress for individuals with low back pain (LBP) in the Military Health System (MHS). We identified common phenotypes defined by rates of general and pain-related psychological distress and compared phenotypes on their level of pain interference, physical function, anxiety, and depression. METHODS: We created a cohort from two completed trials assessing nonpharmacological treatment for LBP in the MHS (n = 510 total). The Optimal Screening for Prediction of Referral and Outcome Yellow Flag assessment tool identified the presence of 11 different yellow flags. Latent class analysis (LCA) used yellow flag indicators to identify common psychological phenotypes. We then compared Patient-Reported Outcomes Measurement Information Systems measures of pain interference, physical function, sleep disturbance, depression, and anxiety across phenotypes. RESULTS: LCA identified five phenotypes (percentage of the sample): low distress (32%), high distress (27%), poor pain coping and low self-efficacy (18%), low self-efficacy and acceptance (14%), and poor pain coping (10%). Highly distressed phenotypes reported higher levels of pain interference, sleep disturbance, depression, and anxiety than those with other phenotypes, whereas the low distress phenotype had significantly lower pain interference and higher physical function scores than those characterized by all other phenotypes. CONCLUSION: These phenotypes provide opportunities for clinicians and researchers to develop novel LBP treatment pathways tailored to patients with different profiles of psychological distress. Future work is needed to validate their predictive capabilities for clinical outcomes.

Acute Intermittent Hypoxia Did Not Alter Pain Sensitivity or Pain Intensity Ratings for Individuals with Chronic Low Back Pain: A Pilot Study.

Aims and Objective: The purpose of this pilot study was to explore whether AIH produces changes in pain sensitivity or in reports of self-reported pain intensity for individuals with low back pain. Methods: In a quasi-experimental, cross-over design we compared participants (n = 9) exposed to normal room air and hypoxia using a commercially available gas blender. The treatment period consisted of 5 consecutive days of randomly assigned to AIH or room air. For the participants initially randomized to AIH there was cross-over to receive 5 more consecutive days of room air. Therefore, this design allowed for between group and within subject assessment of AIH effects. Pain sensitivity was assessed with quantitative sensory testing (QST) for posterior superior iliac spine pressure threshold, plantar thermal threshold, and peak pain ratings. Self-reported pain intensity for low back pain was assessed via the Brief Pain Inventory. Results: There were no between group differences for AIH and room air in pain sensitivity or self-reported pain intensity. In the within subject analyses larger effect sizes favoring AIH were detected for plantar measures of pain sensitivity but not for self-reported pain intensity. Conclusion: This study, while presenting null findings, describes an initial step in determining whether AIH can be used to increase pain relief. Based on this pilot study we offer guidance for future research including study design, AIH dosage, participant selection, and using AIH in combination with non-pharmacologic treatments.

Building Semipermeable Films One Monomer at a Time: Structural Advantages via Molecular Layer Deposition vs Interfacial Polymerization.

Molecular layer deposition (MLD) provides the opportunity to perform condensation polymerization one vaporized monomer at a time for the creation of precise, selective nanofilms for desalination membranes. Here, we compare the structure, chemistry, and morphology of two types of commercial interfacial polymerzation (IP) membranes with lab-made MLD films. M-phenylenediamine (MPD) and trimesoyl chloride (TMC) produced a cross-linked, aromatic polyamide often used in reverse osmosis membranes at MLD growth rates of 2.9 Å/cycle at 115 °C. Likewise, piperazine (PIP) and TMC formed polypiperazine amide, a common selective layer in nanofiltration membranes, with MLD growth rates of 1.5 Å/cycle at 115 °C. Ellipsometry and X-ray reflectivity results suggest that the surface of the MLD films is comprised of polymer segments roughly two monomers in length, which are connected at one end to the cross-linked bulk layer. As a result of this structure as well as the triple-functionality of TMC, MPD-TMC had a temperature window of stable growth rate from 115 to 150 °C, which is unlike any non-cross-linked MLD chemistries reported in the literature. Compared to IP films, corresponding MLD films were denser and morphologically conformal, which suggests a reduction in void volumes; this explains the high degree of salt rejection and reduced flux previously observed for exceptionally thin MPD-TMC MLD membranes. Using X-ray photoelectron spectroscopy and infrared spectroscopy, MLD PIP-TMC films evidenced a completely cross-linked internal structure, which lacked amine and carboxyl groups, pointing to a hydrophobic bulk structure, ideal for optimized water flux. Grazing-incidence wide-angle X-ray scattering showed broad features in each polyamide with d-spacings of 5.0 Å in PIP-TMC compared to that of 3.8 Å in MPD-TMC. While MLD and IP films were structurally identical to PIP-TMC, MPD-TMC IP films had a structure that may have been altered by post-treatment compared to MLD films. These results provide foundational insights into the MLD process, structure-performance relationships, and membrane fabrication.

Nociceptive, neuropathic, or nociplastic low back pain? The low back pain phenotyping (BACPAP) consortium's international and multidisciplinary consensus recommendations.

The potential to classify low back pain as being characterised by dominant nociceptive, neuropathic, or nociplastic mechanisms is a clinically relevant issue. Preliminary evidence suggests that these low back pain phenotypes might respond differently to treatments; however, more research must be done before making specific recommendations. Accordingly, the low back pain phenotyping (BACPAP) consortium was established as a group of 36 clinicians and researchers from 13 countries (five continents) and 29 institutions, to apply a modified Nominal Group Technique methodology to develop international and multidisciplinary consensus recommendations to provide guidance for identifying the dominant pain phenotype in patients with low back pain, and potentially adapt pain management strategies. The BACPAP consortium's recommendations are also intended to provide direction for future clinical research by building on the established clinical criteria for neuropathic and nociplastic pain. The BACPAP consortium's consensus recommendations are a necessary early step in the process to determine if personalised pain medicine based on pain phenotypes is feasible for low back pain management. Therefore, these recommendations are not ready to be implemented in clinical practice until additional evidence is generated that is specific to these low back pain phenotypes.

Hip-focused physical therapy versus spine-focused physical therapy for older adults with chronic low back pain at risk for mobility decline (MASH): a multicentre, single-masked, randomised controlled trial.

BACKGROUND: Previously, we identified a population of older adults with chronic low back pain, hip pain, and hip muscle weakness who had worse 12-month low back pain and functional outcomes than age-matched adults with only low back pain, indicating an increased risk for future mobility decline. We sought to determine whether tailored, hip-focused physical therapy reduced pain and functional limitations in this high-risk population compared with non-tailored, spine-focused physical therapy. METHODS: We did a multicentre, single-masked, randomised controlled trial at three research-based sites in the USA. We recruited older adults (aged 60-85 years) with hip pain and weakness who reported moderate low back pain intensity at least half the days in the last 6 months. Patients were randomly assigned to hip-focused physical therapy or spine-focused physical therapy using permuted blocks with random block size, stratified by site and sex (ie, male or female). The primary outcomes were self-reported disability using the Quebec Back Pain Disability Scale (QBPDS) and performance-based 10-Meter Walk Test (10MWT) at 8 weeks. All analyses were done in the intention-to-treat population. Adverse events were collected by study staff via a possible adverse event reporting form and then adjudicated by site investigators. This trial was registered with ClinicalTrials.gov, NCT04009837. FINDINGS: Between Nov 1, 2019, and April 30, 2022, 184 participants were randomly assigned to receive hip-focused (n=91) or spine-focused physical therapy (n=93) interventions. The mean age was 70·7 (SD 6·2) years. 121 (66%) of 184 participants were women, 63 (34%) were men, and 149 (81%) were White. At 8 weeks, the mean between-group difference on the QBPDS was 4·0 (95% CI 0·5 to 7·5), favouring hip-focused physical therapy. Both groups had similar, clinically meaningful gait speed improvements (10MWT) at 8 weeks (mean difference 0·004 m/s [95% CI -0·044 to 0·052]). No serious adverse events were related to study participation. INTERPRETATION: Tailored hip-focused physical therapy demonstrated greater improvements in low back pain-related disability at 8 weeks. However, both hip-focused physical therapy and spine-focused physical therapy produced clinically meaningful improvements in disability and function for this high-risk population at 6 months. These findings warrant further investigation before clinical implementation. FUNDING: US National Institute on Aging of the National Institutes of Health.

Characterizing Acute Low Back Pain in a Community-Based Cohort.

Acute low back pain (LBP) is a common experience, however, the associated pain severity, pain frequency, and characteristics of individuals with acute LBP in community settings have yet to be well understood. In this manuscript, three acute LBP severity categorization definitions were used based on LBP frequency combined with either 1) pain impact frequency (impact-based) or 2) pain intensity (intensity-based), as well as LBP pain interference frequency (interference only-based) severity categories. The purpose of this manuscript is to describe and then compare these acute LBP severity groups in the following characteristics: 1) sociodemographic, 2) general and physical health, and 3) psychological. This cross-sectional study used baseline data from 131 community-based participants with acute LBP (<4 weeks duration before screening and ≥30 pain-free days before acute LBP onset). Descriptive associations were calculated as prevalence ratios for categorical variables and Hedges' g for continuous variables. Our analyses identified several large associations for impact-based and intensity-based categories with global mental health, global physical health, STarT Back Screening Tool risk category, and general health. Larger associations were found with social constructs (racially and ethnically minoritized, performance of social roles, and isolation) when using the intensity-based versus impact-based categorization. The interference-based category did not capture as much variability between acute LBP severity categories. This study adds to the literature by providing standard ways to characterize community-based individuals experiencing acute LBP. The robust differences observed between these categorization approaches suggest that how we define acute LBP severity is consequential; these different approaches may be used to improve the early identification of factors potentially contributing to the development of chronic LBP.

If You Build It, Will They Come? Patient and Provider Use of a Novel Hybrid Telehealth Care Pathway for Low Back Pain.

OBJECTIVE: The purpose of this study was to describe the referrals and use of a hybrid care model for low back pain that includes on-site care by physical therapists, physical activity training, and psychologically informed practice (PiP) delivered by telehealth in the Improving Veteran Access to Integrated Management of Low Back Pain (AIM-Back) trial. METHODS: Data were collected from November 2020 through February 2023 from 5 Veteran Health Administration clinics participating in AIM-Back, a multisite, cluster-randomized embedded pragmatic trial. The authors extracted data from the Veteran Health Administration Corporate Data Warehouse to describe referral and enrollment metrics, telehealth use (eg, distribution of physical activity and PiP calls), and treatments used by physical therapists and telehealth providers. RESULTS: Seven hundred one veterans were referred to the AIM-Back trial with 422 enrolling in the program (consult-to-enrollment rate = 60.2%). After travel restrictions were lifted, site visits resulted in a significant increase in referrals and a number of new referring providers. At initial evaluation by on-site physical therapists, 92.2% of veterans received pain modulation (eg, transcutaneous electrical nerve stimulation, manual therapy). Over 81% of enrollees completed at least 1 telehealth physical activity call, with a mean of 2.8 (SD = 2.0) calls out of 6. Of the 167 veterans who screened as medium to high risk of persistent disability, 74.9% completed at least 1 PiP call, with a mean of 2.5 (SD = 2.0) calls out of 6. Of those who completed at least 1 PiP call (n = 125), 100% received communication strategies, 97.6% received pain coping skills training, 89.6% received activity-based treatments, and 99.2% received education in a home program. CONCLUSION: In implementing a hybrid care pathway for low back pain, the authors observed consistency in the delivery of core components (ie, pain modulation, use of physical activity training, and risk stratification to PiP), notable variability in telehealth calls, high use of PiP components, and increased referrals with tailored provider engagement. IMPACT: These findings describe variability occurring within a hybrid care pathway and can inform future implementation efforts.

A vascularized 3D model of the human pancreatic islet forex vivostudy of immune cell-islet interaction.

Insulin is an essential regulator of blood glucose homeostasis that is produced exclusively byßcells within the pancreatic islets of healthy individuals. In those affected by diabetes, immune inflammation, damage, and destruction of isletßcells leads to insulin deficiency and hyperglycemia. Current efforts to understand the mechanisms underlyingßcell damage in diabetes rely onin vitro-cultured cadaveric islets. However, isolation of these islets involves removal of crucial matrix and vasculature that supports islets in the intact pancreas. Unsurprisingly, these islets demonstrate reduced functionality over time in standard culture conditions, thereby limiting their value for understanding native islet biology. Leveraging a novel, vascularized micro-organ (VMO) approach, we have recapitulated elements of the native pancreas by incorporating isolated human islets within a three-dimensional matrix nourished by living, perfusable blood vessels. Importantly, these islets show long-term viability and maintain robust glucose-stimulated insulin responses. Furthermore, vessel-mediated delivery of immune cells to these tissues provides a model to assess islet-immune cell interactions and subsequent islet killing-key steps in type 1 diabetes pathogenesis. Together, these results establish the islet-VMO as a novel,ex vivoplatform for studying human islet biology in both health and disease.

Effect of a Patient Engagement, Education, and Restructuring of Cognitions (PEERC) approach on conservative care in rotator cuff related shoulder pain treatment: a randomized control trial.

BACKGROUND: Despite similar outcomes for surgery and physical therapy (PT), the number of surgeries to treat rotator cuff related shoulder pain (RCRSP) is increasing. Interventions designed to enhance treatment expectations for PT have been shown to improve patient expectations, but no studies have explored whether such interventions influence patient reports of having had surgery, or being scheduled for surgery. The purpose of this randomized clinical trial was to examine the effect of a cognitive behavioral intervention aimed at changing expectations for PT on patient-report of having had or being scheduled for surgery and on the outcomes of PT. METHODS: The Patient Engagement, Education, and Restructuring of Cognitions (PEERC) intervention, was designed to change expectations regarding PT. PEERC was evaluated in a randomized, pragmatic "add-on" trial in by randomizing patients with RCRSP to receive either PT intervention alone (PT) or PT + PEERC. Fifty-four (54) individuals, recruited from an outpatient hospital-based orthopedic clinic, were enrolled in the trial (25 randomized to PT, 29 randomized to PT + PEERC). Outcomes assessed at enrollment, 6 weeks, discharge, and six months after discharge included the patient report of having had surgery, or being scheduled for surgery (primary) and satisfaction with PT outcome, pain, and function (secondary outcomes). RESULTS: The average age of the 54 participants was 51.81; SD = 12.54, and 63% were female. Chronicity of shoulder pain averaged 174.61 days; SD = 179.58. Study results showed that at the time of six months follow up, three (12%) of the participants in the PT alone group and one (3.4%) in the PT + PEERC group reported have had surgery or being scheduled for surgery (p = .32). There were no significant differences between groups on measures of satisfaction with the outcome of PT (p = .08), pain (p = .58) or function (p = .82). CONCLUSIONS: In patients with RCRSP, PT plus the cognitive behavioral intervention aimed at changing expectations for PT provided no additional benefit compared to PT alone with regard to patient report of having had surgery, or being scheduled to have surgery, patient reported treatment satisfaction with the outcome of PT, or improvements in pain, or function. TRIAL REGISTRATION: The trial is registered on ClinicalTrials.gov: NCT03353272 (27/11/2017).