Sara Elizabeth Williams

All Publications

• Development of a core outcome set for clinical trials of extended reality for pain. Pain reports Mesaroli, G., Hess, C. W., Alam, F., Baker, N. A., Colloca, L., Eccleston, C., Harris, L., King, C., Linkiewich, D., Olaizola, S., Poonai, N., Pope, N., Rosenbloom, B. N., Stanton, T. R., Trost, Z., Williams, S. E., Simons, L. E., Logan, D., Stinson, J. N. 2026; 11 (4): e1470

  Abstract

  The number of clinical trials of extended reality (XR), including virtual and augmented reality, for pain has exponentially increased in the past 2 decades. To synthesize findings across studies and assess the effectiveness of XR interventions, a core outcome set (COS) is needed. Prior work identified 7 core outcome domains for XR trials in pain through a systematic review and consensus process.The aim of this study was to establish a finalized COS of outcome measures (adult and pediatric) for XR trials for pain (acute, recurrent, and chronic).First, potential outcome measures were identified for each core domain through literature reviews. Second, a Delphi study was conducted with experts who rated suitability of each measure. Third, an expert consensus conference (including clinicians, researchers, and people with lived experience) was held to review the measurement properties of each candidate measure and to vote on a final COS of measures for XR.A total of 52 experts participated in the Delphi survey and 15 attended the consensus conference. Among participants, 8 (52%) specialised in pediatric populations, 5 (33%) in adult populations, and 2 (15%) across the lifespan. Within each outcome domain, 2 to 4 measures with the highest rated suitability were selected as candidates. Consensus was achieved on a final COS consisting of 10 measures for pediatric trials and 8 for adult trials.This is a promising and necessary step to advance the field of XR pain research and better understand the effectiveness of XR for pain.

  View details for DOI 10.1097/PR9.0000000000001470

  View details for PubMedID 42416554

  View details for PubMedCentralID PMC13340730

• A psychometric investigation of performance-based and self-report measures in a pediatric population with chronic pain: How well do these measures work? PM & R : the journal of injury, function, and rehabilitation Williams, S. E., Crowley, S. L., Collins, A. B., Pruitt, D. W., John, A., Samuel, N. D., Deet, E. T., Szabova, A., Homan, K. J. 2026

  Abstract

  Traditional rehabilitation measures, such as the Functional Independence Measure for Children (WeeFIM II), designed to measure the need for assistance and severity of disability in children with developmental disabilities, may not be an optimal indicator of physical function among pediatric patients with chronic pain undergoing rehabilitation. A better understanding of the ability of physical outcome measures to detect change over time would improve evaluation of patient response to pain interventions such as intensive interdisciplinary pain treatment (IIPT).To investigate the responsiveness to intervention of commonly used functional assessments among pediatric patients with pain undergoing IIPT.This retrospective cohort study collected self-reported and performance-based measures at admission and discharge from an IIPT program. The institutional review board approved study procedures.IIPT program in an inpatient pediatric rehabilitation unit at a major midwestern children's hospital in the United States.Demographics and clinical outcomes from 210 patients admitted between January 2014 and December 2022 were abstracted from the medical record. Patients were 9-19 years old (average age = 15), 75% were female, and 91% were White. The most common diagnosis was amplified musculoskeletal pain syndrome (26%).Patients attended an IIPT program for an average of 17 days and completed measures at admission and discharge.Four performance-based measures, WeeFIM II, Bruininks-Oseretsky Test of Motor Proficiency (BOT-2), 30-second step test (30SST), grip strength, and 6-minute walk test (6MWT), and one self-report measure, Canadian Occupational Performance Measure (COPM).Self-reported COPM and performance-based 6MWT and 30SST scores showed the greatest responsiveness to intervention. The WeeFIM II and BOT-2 scores were the least responsive to intervention.The COPM, 6MWT, 30SST were the most responsive measures to intervention, capturing improvement among children with chronic pain completing an IIPT program; the WeeFIM II and BOT-2 were the least responsive measures to intervention for this population.

  View details for DOI 10.1002/pmrj.70152

  View details for PubMedID 42152171

• From Routine to Results: Greater Behavioral Adherence Predicts Better Clinical Outcomes in Treatment of Pediatric Chronic Musculoskeletal Pain Hale, M., Peugh, J., Connelly, M., Goldstein-Leever, A., Kirschman, M., Klages, K., Logan, D., Nelson, S., Wakefield, E., Williams, A., Williams, S., Kashikar-Zuck, S. OXFORD UNIV PRESS INC. 2026: 2-3

  View details for Web of Science ID 001744393400222

• Multicenter randomized controlled trial of cognitive-behavioral, exercise-based, and combined interventions for juvenile fibromyalgia. Pain Kashikar-Zuck, S., Williams, S. E., Ittenbach, R. F., Peugh, J., Thomas, S., Lynch-Jordan, A. M., Kirschman, M., Ting, T. V., Connelly, M., Zempsky, W., Williams, A. E., Ardoin, S. P., Logan, D. E., Wakefield, E. O., Goldstein-Leever, A., Goldschneider, K., Nelson, S., Stinson, J. N., Myer, G. D. 2026; 167 (4): 820-831

  Abstract

  Juvenile fibromyalgia (JFM) is a complex and disabling chronic pain condition for which treatment options are limited. The objective of this randomized controlled trial was to compare the relative efficacy of 3 group-based interventions: cognitive-behavioral therapy (CBT) alone, graded aerobic exercise (GAE) alone, or CBT combined with specialized neuromuscular exercise (Fibromyalgia Integrative Training [FIT] Teens), in reducing pain-related disability for adolescents with JFM. Patients with JFM (ages 12-17) who experienced moderate-to-severe pain and pain-related disability were eligible. A total of 317 adolescents (86.4% girls, 84.2% White, mean age 15.8 years) were randomized to receive 8 weeks (16 sessions) of CBT (N = 110), GAE (N = 104), or FIT Teens (N = 103), followed by 4 booster sessions. Our primary hypothesis that the FIT Teens intervention would be superior to CBT or GAE was not supported. Rather, participants in all treatments showed significant reduction in disability with no differences between groups at the 3-month primary endpoint (main effect estimate = -3·94 [95% CI: -6·62 to -1·26]) and at 6-, 9-, and 12-month follow-up (main effect estimate = -4·52 [95% CI: -7·35 to -1·68]; -4·21 [95% CI: -7·13 to -1·29]; and -4·76 [95% CI: -7·84 to -1·68], respectively). Pain intensity was significantly improved at 9- and 12-month follow-up. Although the overall magnitude of improvement in disability was small, approximately 1 in 4 patients in the FIT and CBT groups had clinically remarkable improvement. Cognitive-behavioral and exercise-based treatments are promising for the management of JFM. Further research is needed to examine the characteristics of treatment responders and the mechanisms of improvement.

  View details for DOI 10.1097/j.pain.0000000000003840

  View details for PubMedID 41852282

• Virtual Reality for the Management of Postoperative Pain and Anxiety in Children and Adolescents Undergoing Nuss Repair of Pectus Excavatum: Randomized Controlled Trial. JMIR perioperative medicine Walter, C. M., Froass, D., Bell, N., Haack, L., Boehmer, C., Bruguera Torres, C., Spivak, R., Chou, M., Geisler, K., O'Conor, K., Williams, S. E., Ding, L., King, C. D., Olbrecht, V. A. 2026; 9: e80902

  Abstract

  Virtual reality (VR) is a novel technology with implications for pain and sensory processing. VR may serve as a novel, scalable method to deliver clinically validated therapy for pain management as an alternative or adjunct to opioids for acute pain. Given that psychological factors and pain perception are both components of postoperative pain, it may also be beneficial to incorporate modalities that decrease anxiety, such as active relaxation and guided meditation with VR. Unfortunately, these therapies are not widely available due to multiple barriers. VR has the potential to deliver pain-reducing, psychologically based therapy to children, thereby enhancing multimodal analgesia and potentially decreasing opioid use. This study investigates the role of VR in reducing pain and anxiety after surgery. Given the substantial risks associated with opioid use, particularly in younger populations, alternative pain management strategies are crucial.The primary aim of this study was to evaluate the efficacy of VR as a nonpharmacological intervention for managing postoperative pain intensity, pain unpleasantness, anxiety, and opioid use in children and adolescents undergoing Nuss repair of pectus excavatum.A single-center, prospective, randomized, controlled trial was conducted at a tertiary care children's hospital and research center. Ninety children and adolescents (8-18 y) undergoing the Nuss procedure were randomized to guided relaxation or mindfulness VR (n=30) and distraction-based gaming VR (n=30), combined to form the VR group (n=60), and a control group using a passive 360° video (n=30). Patients received a 10-minute session on postoperative days 1 and 2. Pain intensity, pain unpleasantness, and anxiety were evaluated before and 0-, 15-, and 30-minute post-session. In-hospital pain scores, anxiety scores, and opioid use were collected.Children and adolescents who participated in VR reported a significantly greater decrease in pain intensity from baseline (0.41, SE 0.23) compared with those in the 360° video group at 30 minutes (P=.04) before multiplicity adjustment but not after multiplicity adjustment. There were no significant differences in pain scores or opioid use between the VR and control groups on postoperative day 1 or 2, nor were there changes in pain unpleasantness or anxiety at any time after the intervention.Daily, 10-minute VR sessions provided some trends toward transient analgesic and anxiolytic effects, albeit none that were statistically significant. VR did not significantly decrease overall pain scores or opioid usage, possibly due to the limited intervention duration and high standardized opioid use. Future studies should investigate extended and more frequent VR sessions and the integration of VR with other therapeutic modalities.

  View details for DOI 10.2196/80902

  View details for PubMedID 41805632

  View details for PubMedCentralID PMC12974358

• Data Validation of a Biofeedback-Based Virtual Reality Technology for Pediatric Pain and Anxiety Reduction Heisterberg, L. M., Abdallah, C. G., Orgil, Z., Woodrum, L., Ding, L., Kashikar-Zuck, S., King, C. D., Williams, S. E., Olbrecht, V. A. LIPPINCOTT WILLIAMS & WILKINS. 2024: 1496-1497

  View details for Web of Science ID 001367242803156

• Understanding Patient Acceptability, Engagement, and Motivation in Guided Relaxation-Based Virtual Reality Therapy for Pediatric Pain and Anxiety Orgil, Z., Lo, C., Heisterberg, L. M., Karthic, A., Woodrum, L., Abdallah, C. G., Ding, L., Kashikar-Zuck, S., King, C. D., Williams, S. E., Olbrecht, V. A. LIPPINCOTT WILLIAMS & WILKINS. 2024: 1467-1469

  View details for Web of Science ID 001367242803143

• "Virtual reality fixed me": A case report of the use of virtual reality during intensive interdisciplinary pain treatment. Journal of pediatric rehabilitation medicine King, C. D., Olbrecht, V. A., Crowley, S. L., Klages, K. L., Deet, E. T., Samuel, N. D., Smith, K., Williams, S. E., Homan, K. J. 2024

  Abstract

  Virtual reality (VR) is an innovative technology with the potential to enhance treatment for children with chronic pain and functional symptoms. Currently, little is known about patients' experiences of VR in the setting of intensive interdisciplinary pain treatment (IIPT). This study aimed to better understand how patients engage with and benefit from VR. This case report focuses on a 12-year-old female with amplified musculoskeletal pain syndrome and comorbid functional neurological disorder receiving treatment in inpatient IIPT. VR was incorporated into physical/occupational and recreational therapy sessions. A semi-structured interview was completed one-month post-discharge. Qualitative analysis revealed three major themes: Process of Change (VR was unique/immersive, reduced pain focus, challenged skepticism, and changed pain perception), Efficacy (VR increased movement, supported transitioning from a wheelchair to walking independently, and increased confidence, excitement, and surprise), and Engagement (VR aided in acknowledging progress, increased camaraderie, was fun, and challenged patient to extend treatment goals made in VR to real life). Therapist observations of the benefits and barriers to using VR in treatment are described. Overall, this report indicates that VR may be a helpful tool to use with existing IIPT interventions to enhance patient engagement in treatment and improve functionaloutcomes.

  View details for DOI 10.3233/PRM-230059

  View details for PubMedID 39150838

• A systematic cognitive behavioral therapy approach for pediatric disorders of gut-brain interaction. Neurogastroenterology and motility Chancey, L. P., Winnick, J. B., Buzenski, J., Winberry, G., Stiles, A., Zahka, N. E., Williams, S. E. 2024: e14883

  Abstract

  OBJECTIVE: Cognitive Behavioral Therapy (CBT) for youth with Disorders of Gut-Brain Interaction (DGBIs) is effective; however, there are calls in the field to strengthen the evidence base and identify specific mechanisms of treatment that yield the most benefit for this patient population. A unique, systematic treatment approach of CBT with initial evidence for success for pediatric patients with DGBIs was evaluated to further demonstrate its clinical utility in this population.METHODS: This was a retrospective study of 42 pediatric patients aged 11-17years with DGBIs, who were diagnosed and referred for CBT by pediatric gastroenterology providers. Providers also completed a survey rating acceptability and effectiveness of CBT. The systematic CBT approach included 10 sessions delivered by a psychologist at an integrated Pediatric GI Clinic.RESULTS: Review of 42 pediatric charts showed significant decreases in self-reported functional disability, abdominal pain, as well as depression and anxiety symptoms pre- to post-CBT completion. A moderation effect was observed where patients reporting higher levels of depressive symptoms and primary symptom of abdominal pain reported smaller reductions in functional impairment compared to those with lower levels of depression and primary symptom of nausea or vomiting. Pediatric Gastroenterology providers were satisfied with this psychological treatment approach.CONCLUSIONS: This study provides evidence for acceptability and effectiveness of implementation of a systematic CBT approach for pediatric DGBIs in an integrated GI clinic, as well as areas worthy of future research, including identifying the most important mechanisms of treatment and factors that influence treatment response.

  View details for DOI 10.1111/nmo.14883

  View details for PubMedID 39099152

• The need for a true biofeedback-based virtual reality system for achievement of target heart rate variability for children undergoing surgery. Paediatric anaesthesia Orgil, Z., Heisterberg, L. M., Froass, D., Karthic, A., Williams, S. E., Ding, L., Kashikar-Zuck, S., King, C. D., Olbrecht, V. A. 2024

  View details for DOI 10.1111/pan.14887

  View details for PubMedID 38567441

• Feasibility and Acceptability of Biofeedback-Based Virtual Reality System Use in Children and Adolescents Undergoing Surgery: Phase 1 of a Pilot Observational Study. JMIR perioperative medicine Orgil, Z., Karthic, A., Bell, N. F., Heisterberg, L. M., Williams, S. E., Ding, L., Kashikar-Zuck, S., King, C. D., Olbrecht, V. A. 2024

  Abstract

  BACKGROUND: Biofeedback-based virtual reality (VR-BF) is a novel, nonpharmacologic method for teaching patients how to control their breathing, which in turn increases heart rate variability (HRV) and may reduce pain. Unlike traditional forms of biofeedback (BF), VR-BF is delivered through a gamified virtual reality environment, increasing the accessibility of BF. This is the first study to systematically integrate VR-BF use in the pediatric perioperative setting, with the ultimate goal of evaluating the efficacy of VR-BF to reduce pain, anxiety, and opioid consumption once feasibility and acceptability has been established.OBJECTIVE: The primary objective was to develop a clinical trial protocol for VR-BF use in the pediatric perioperative setting, including preoperative education/training and postoperative application of VR-BF in children undergoing surgery. A secondary objective was to evaluate the patient/parent experience with VR-BF.METHODS: A total of 23 patients (12-18 years of age) scheduled for surgery at Nationwide Children's Hospital were recruited using purposive sampling. Following training, participants independently completed a daily, 10-minute VR-BF session for seven days before surgery and during their inpatient stay. Participants could use VR-BF up to two weeks after hospital discharge. Patient and session-level data of VR-BF usage and achievement of target HRV parameters were measured to identify the optimal frequency and duration of sessions before and after surgery for this population. Standardized questionnaires and semi-structured interviews were conducted to obtain qualitative information about patients' experiences with VR-BF.RESULTS: Patient-level data indicated that the highest odds of achieving 1 session under target HRV parameters was after 4 sessions (OR 4 vs. 3 sessions=5.1, 95% CI 1.3-20.6; OR 3 vs. 2 sessions=16.6, 95% CI 1.2-217.0). Session-level data showed that a session duration of 9 to 10 minutes provided the greatest odds of achieving 1 session under target HRV parameters (OR 9 vs. 8 minutes=1.3, 95% CI 1.1-1.7; OR 8 vs. 7 minutes=1.4, 95% CI 1.1-1.8; OR 10 vs. 9 minutes=1.0, 95% CI 0.9-1.2). Qualitative data revealed patient satisfaction with the VR-BF technology, particularly in managing perioperative stress (n=17, 85%). Few patients reported VR-BF as beneficial for pain (n=8, 40%).CONCLUSIONS: Children and adolescents undergoing surgery successfully learned behavioral strategies with VR-BF with once-daily 10-minute sessions for 5 days. To integrate VR-BF as a therapeutic intervention in a subsequent clinical trial, patients will be instructed to complete three 10-minute sessions a day for 7 days after surgery.CLINICALTRIAL: ClinicalTrials.gov; NCT04943874; https://clinicaltrials.gov/ct2/show/NCT04943874.

  View details for DOI 10.2196/48959

  View details for PubMedID 38742940

• Understanding Treatment Trajectories of Patients with Functional Neurological Disorder in Intensive Interdisciplinary Pain Treatment: A Case Series Brabson, L., Ma, R., Harrison, L. E., Hess, C. W., Webb, W., Majmundar, S., Wagner, J., Williams, S. E., Griffin, A. OXFORD UNIV PRESS INC. 2024: 75

  View details for Web of Science ID 001271423400153

• A narrative review of the literature on illness uncertainty in hypermobile ehlers-danlos syndrome: implications for research and clinical practice. Pediatric rheumatology online journal Feldman, E. C., Homan, K. J., Williams, S. E., Ting, T. V., Goldschneider, K. R., Kashikar-Zuck, S. 2023; 21 (1): 121

  Abstract

  Hypermobile Ehlers-Danlos syndrome (hEDS) is characterized by joint and skin laxity, and often accompanied by chronic pain, dysautonomia, increased distress and, functional limitations. The journey to accurate diagnosis is often prolonged due to unclear etiology of symptoms. This manuscript is a narrative review of the literature on illness uncertainty (IU) in hEDS, highlighting the unique facets of IU in this population, as compared to the broader chronic pain population (given symptom overlap between these two disease groups), that warrant additional investigation. Additionally, we considered the unique challenges associated with IU in the context of the developmental nuances of pediatric populations. Specifically, we aimed to (1) map the extant literature of the IU experience in chronic pain conditions broadly including the pediatric and adult research to identify key concepts related to IU and incorporate potential developmental considerations in IU; (2) delineate and describe the IU experience specifically in patients with hEDS, with the goal of identifying gaps in the literature based on aspects of presentation in hEDS that do and do not differ from the broader chronic pain population; and (3) elucidate the potential areas of adverse impact of IU in both general chronic pain populations, and those with hEDS specifically, to provide actionable areas for future research and clinical care of individuals with hEDS. Results of this review indicate that IU has been well-studied in chronic pain generally, but inadequately evaluated in hEDS specifically. Specific features of hEDS (complexity of the disorder, involvement of multiple bodily systems, contribution of organic pathology) may uniquely contribute to IU in this population. This review suggests that ambiguities surrounding the diagnosis of hEDS, symptom course, and treatment recommendations, along with misdiagnosis, perceived dismissal of symptoms, or attribution of symptoms to mental health concerns might increase risk for IU and related distress in patients.Findings from the present review suggest that distinct features of hEDS yield a set of driving factors for IU that may be somewhat different than those faced by patients with chronic pain or other medical conditions. The development of a validated measure of IU to appropriately assess this construct in patients with hEDS is a research priority. In the clinical setting, providers should be attentive to the potentially aversive diagnostic and treatment experiences reported by patients and attempt to provide clear explanations based on the extant knowledge of hEDS, and implement best-practice recommendations for multidisciplinary treatment.

  View details for DOI 10.1186/s12969-023-00908-6

  View details for PubMedID 37845704

  View details for PubMedCentralID PMC10577933

• Dataset used to refine a treatment protocol of a biofeedback-based virtual reality intervention for pain and anxiety in children and adolescents undergoing surgery DATA IN BRIEF Orgil, Z., Karthic, A., Bell, N., Williams, S. E., Ding, L., Kashikar-Zuck, S., King, C. D., Olbrecht, V. A. 2023; 49: 109331

  Abstract

  There is a great need for nonpharmacologic pain management strategies, given the catastrophic effects of the opioid epidemic and the role of opioid prescription in precipitating addiction [1], particularly in children and adolescents at risk of chronic pain and opioid use after surgery [2], [3], [4]. Biofeedback-based virtual reality (VR-BF) is an innovative approach to managing pain that compliments and may even increase accessibility [5] and acceptability [6] of existing mind-body therapies for pain management, like biofeedback (BF). BF teaches patients behavioral modification techniques that impact involuntary processes [7,8]. For example, slow breathing increases heart rate variability (HRV) [9] to reduce pain through the downregulation of the sympathetic nervous system [10,11]. However, barriers to widespread use, such as the need for trained personnel and high costs of direct intervention, have hindered its widespread clinical use and access to this therapy [5,12]. VR-BF has not yet been integrated into perioperative care, and as such, no defined treatment protocols for preoperative training and postoperative application of VR-BF exist, particularly in children. The dataset presented in this article may help fill the unmet, critical need for accessible, effective, alternative therapeutic options for reducing postoperative pain and opioid exposure in children. This investigation aimed to establish measurable outcomes impacting a perioperative treatment protocol of VR-BF, a novel VR-based therapy that teaches patients relaxation techniques and monitors the sensitivity of heart rate variability (HRV) to different frequencies and durations of VR-BF sessions. Achievement of target physiological parameters, including HRV, was measured in children and adolescents undergoing surgery anticipated to cause moderate to severe pain (e.g., orthopedic, chest) requiring postoperative pain management by the Acute Pain Services at Nationwide Children's Hospital (NCH). This dataset included 23 surgical patients evaluated quantitatively and qualitatively to refine a treatment protocol for the feasibility and acceptability of (a) preoperative education and training in relaxation, and (b) postoperative application of a VR-BF intervention for pain management [13]. Qualitative data was collected using an investigator-derived questionnaire to obtain feedback and understand the patient and family experience using VR-BF. Descriptive statistics (mean±SD or median with interquartile range [IQR] for continuous variables; frequencies and percentages for categorical variables) and exploratory spline regression analyses were generated to define measurable outcomes for a future pilot, randomized clinical trial protocol.

  View details for DOI 10.1016/j.dib.2023.109331

  View details for Web of Science ID 001027852500001

  View details for PubMedID 37456123

  View details for PubMedCentralID PMC10338292

• FIT Teens RCT for juvenile fibromyalgia: Protocol adaptations in response to the COVID 19 pandemic CONTEMPORARY CLINICAL TRIALS COMMUNICATIONS Kashikar-Zuck, S., Barnett, K. A., Williams, S. E., Pfeiffer, M., Thomas, S., Beasley, K., Chamberlin, L., Mundo, K., Ittenbach, R. F., Peugh, J., Gibler, R. C., Lynch-Jordan, A., Ting, T., Gadd, B., Taylor, J., Goldstein-Leever, A., Connelly, M., Logan, D. E., Williams, A., Wakefield, E. O., Myer, G. D. 2022; 30: 101039

  Abstract

  To describe protocol adaptations to the Fibromyalgia Integrative Training for Teens (FIT Teens) randomized controlled trial in response to the COVID-19 pandemic. The overarching aims of the FIT Teens multi-site 3-arm comparative effectiveness trial are to assess whether a specialized neuromuscular exercise training intervention combined with cognitive-behavioral therapy (CBT) is superior to CBT alone or graded aerobic exercise alone.The trial was originally designed as an in-person, group-based treatment with assessments at baseline, mid- and post-treatment, and four follow-up time points. The original study design and methodology was maintained with specific modifications to screening, consenting, assessments, and group-based treatments to be delivered in remote (telehealth) format in response to COVID-19 restrictions.Study enrollment was paused in March 2020 for five months to revise operations manuals, pilot remote treatment sessions for accuracy and fidelity, complete programming of REDCap assent/consent and assessment materials, train study staff for new procedures and obtain regulatory approvals. The trial was relaunched and has been successfully implemented in remote format since July 2020. Trial metrics thus far demonstrate a consistent rate of enrollment, strong attendance at remote treatment sessions, high retention rates and high treatment fidelity after protocol adaptations were implemented.Preliminary findings indicate that FIT Teens protocol adaptations from in-person to remote are feasible and allowed for sustained enrollment, retention, and treatment fidelity comparable to the in-person format. Methodologic and statistical considerations resulting from the adaptations are discussed as well as implications for interpretation of results upon completion of the trial.

  View details for DOI 10.1016/j.conctc.2022.101039

  View details for Web of Science ID 000897255000003

  View details for PubMedID 36467389

  View details for PubMedCentralID PMC9707024

• Signature for Pain Recovery IN Teens (SPRINT): protocol for a multisite prospective signature study in chronic musculoskeletal pain. BMJ open Simons, L., Moayedi, M., Coghill, R. C., Stinson, J., Angst, M. S., Aghaeepour, N., Gaudilliere, B., King, C. D., López-Solà, M., Hoeppli, M. E., Biggs, E., Ganio, E., Williams, S. E., Goldschneider, K. R., Campbell, F., Ruskin, D., Krane, E. J., Walker, S., Rush, G., Heirich, M. 2022; 12 (6): e061548

  Abstract

  Current treatments for chronic musculoskeletal (MSK) pain are suboptimal. Discovery of robust prognostic markers separating patients who recover from patients with persistent pain and disability is critical for developing patient-specific treatment strategies and conceiving novel approaches that benefit all patients. Given that chronic pain is a biopsychosocial process, this study aims to discover and validate a robust prognostic signature that measures across multiple dimensions in the same adolescent patient cohort with a computational analysis pipeline. This will facilitate risk stratification in adolescent patients with chronic MSK pain and more resourceful allocation of patients to costly and potentially burdensome multidisciplinary pain treatment approaches.Here we describe a multi-institutional effort to collect, curate and analyse a high dimensional data set including epidemiological, psychometric, quantitative sensory, brain imaging and biological information collected over the course of 12 months. The aim of this effort is to derive a multivariate model with strong prognostic power regarding the clinical course of adolescent MSK pain and function.The study complies with the National Institutes of Health policy on the use of a single internal review board (sIRB) for multisite research, with Cincinnati Children's Hospital Medical Center Review Board as the reviewing IRB. Stanford's IRB is a relying IRB within the sIRB. As foreign institutions, the University of Toronto and The Hospital for Sick Children (SickKids) are overseen by their respective ethics boards. All participants provide signed informed consent. We are committed to open-access publication, so that patients, clinicians and scientists have access to the study data and the signature(s) derived. After findings are published, we will upload a limited data set for sharing with other investigators on applicable repositories.NCT04285112.

  View details for DOI 10.1136/bmjopen-2022-061548

  View details for PubMedID 35676017

• Healthcare utilization among youth with Ehlers-Danlos syndrome hypermobile type AMERICAN JOURNAL OF MEDICAL GENETICS PART A Williams, S. E., Tran, S. T., Lynch-Jordan, A., Goldschneider, K. R., Ting, T., Kashikar-Zuck, S., Neilson, D. 2022; 188 (4): 1109-1117

  Abstract

  Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited disorders of connective tissue. EDS hypermobility type (EDS-HT), characterized by joint hypermobility, is most common and increasingly recognized in pediatrics. Treatment involves protecting joints, preventing injuries, and managing symptoms/comorbidities. Pediatric EDS-HT patients often see multiple medical providers; however, data on healthcare utilization (HCU) in this population are lacking. This retrospective, electronic chart review examines HCU data 1 year prior and subsequent to a new diagnosis of EDS-HT using Villefranche criteria. Demographics, diagnoses, and HCU (office visits, therapies, hospital encounters/procedures, and tests) were obtained for N = 102 youth attending a Connective Tissue Disorder Clinic over a 21-month timeframe. After EDS-HT diagnosis, HCU patterns shifted to reflect greater involvement of therapy (physical, psychological, and occupational) and symptom management. More genetics, rheumatology, and orthopedics visits occurred prediagnosis, and more physical therapy, pain management, cardiology, and neurology visits occurred postdiagnosis. Testing and hospital encounter/procedure frequencies did not change. Overall, the pattern of HCU changed from diagnostic to treatment, in accordance with evidence-based EDS-HT care. Understanding HCU patterns of pediatric patients with EDS-HT can elucidate patient interaction with the health care system, with the potential to inform and improve the standard of care.

  View details for DOI 10.1002/ajmg.a.62625

  View details for Web of Science ID 000739332900001

  View details for PubMedID 34989147

• Guided Relaxation-Based Virtual Reality for Acute Postoperative Pain and Anxiety in a Pediatric Population: Pilot Observational Study JOURNAL OF MEDICAL INTERNET RESEARCH Olbrecht, V. A., O'Conor, K. T., Williams, S. E., Boehmer, C. O., Marchant, G. W., Glynn, S. M., Geisler, K. J., Ding, L., Yang, G., King, C. D. 2021; 23 (7): e26328

  Abstract

  Distraction-based therapies, such as virtual reality (VR), have been used to reduce pain during acutely painful procedures. However, distraction alone cannot produce prolonged pain reduction to manage sustained postoperative pain. Therefore, the integration of VR with other pain-reducing therapies, like guided relaxation, may enhance its clinical impact.The goal of this pilot study was to assess the impact of a single guided relaxation-based VR (VR-GR) session on postoperative pain and anxiety reduction in children. We also explored the influence of pain catastrophizing and anxiety sensitivity on this association.A total of 51 children and adolescents (7-21 years) with postoperative pain and followed by the Acute Pain Service at Cincinnati Children's Hospital were recruited over an 8-month period to undergo a single VR-GR session. Prior to VR, the patients completed 2 questionnaires: Pain Catastrophizing Scale for Children (PCS-C) and the Child Anxiety Sensitivity Index (CASI). The primary outcome was a change in pain intensity following the VR-GR session (immediately, 15 minutes, and 30 minutes). The secondary outcomes included changes in pain unpleasantness and anxiety.The VR-GR decreased pain intensity immediately (P<.001) and at 30 minutes (P=.04) after the VR session, but not at 15 minutes (P=.16) postsession. Reductions in pain unpleasantness were observed at all time intervals (P<.001 at all intervals). Anxiety was reduced immediately (P=.02) but not at 15 minutes (P=.08) or 30 minutes (P=.30) following VR-GR. Patients with higher CASI scores reported greater reductions in pain intensity (P=.04) and unpleasantness (P=.01) following VR-GR. Pain catastrophizing was not associated with changes in pain and anxiety.A single, short VR-GR session showed transient reductions in pain intensity, pain unpleasantness, and anxiety in children and adolescents with acute postoperative pain. The results call for a future randomized controlled trial to assess the efficacy of VR-GR.ClinicalTrials.gov NCT04556747; https://clinicaltrials.gov/ct2/show/NCT04556747.

  View details for DOI 10.2196/26328

  View details for Web of Science ID 000672547200008

  View details for PubMedID 34048358

  View details for PubMedCentralID PMC8314162

• Transient Reductions in Postoperative Pain and Anxiety with the Use of Virtual Reality in Children PAIN MEDICINE Olbrecht, V. A., O'Conor, K. T., Williams, S. E., Boehmer, C. O., Marchant, G. W., Glynn, S. M., Geisler, K. J., Pickerill, H. M., Ding, L., Yang, G., King, C. D. 2021; 22 (11): 2426-2435

  Abstract

  Virtual reality is a promising method to manage pain. Distraction-based virtual reality (VR-D) is thought to reduce pain by redirecting attention. Although VR-D can reduce pain associated with acutely painful procedures, it is unclear whether VR-D can reduce pain after surgery. We assessed the ability of a single VR-D session to decrease postoperative pain and anxiety and explored whether pain catastrophizing and anxiety sensitivity influenced these outcomes in children after surgery.Single-center, prospective, pilot study.Cincinnati Children's Hospital Medical Center (CCHMC).Fifty children (7-21 years of age) with postoperative pain followed by the Acute Pain Service.Patients received one VR-D session after surgery. Before the session, patients completed pain catastrophizing (Pain Catastrophizing Scale for Children) and anxiety sensitivity (Child Anxiety Sensitivity Index) questionnaires. The primary outcome consisted of changes in pain intensity after VR-D (immediately, 15 minutes, and 30 minutes). Secondary outcomes included changes in pain unpleasantness and anxiety.VR-D use was associated with a decrease in pain intensity immediately and 15 minutes after VR-D. Reductions in pain unpleasantness were observed up to 30 minutes after VR-D. VR-D was also associated with a reduction in anxiety immediately and at 15 minutes. Although patients with higher pain catastrophizing had higher baseline pain intensity and unpleasantness, they did not show larger pain reductions after VR-D than those with lower pain catastrophizing.VR-D may be beneficial in transiently reducing pain intensity, unpleasantness, and anxiety in children with postoperative pain. This study informs the design of a larger, randomized, controlled study assessing VR-D for acute postoperative pain and anxiety management.

  View details for DOI 10.1093/pm/pnab209

  View details for Web of Science ID 000743612000003

  View details for PubMedID 34175959

• Improvements in Sleep Correlate With Improvements in Clinical Outcomes Among Adolescents Undergoing Intensive Interdisciplinary Pain Treatment CLINICAL JOURNAL OF PAIN Boggero, I. A., Krietsch, K. N., Pickerill, H. M., Byars, K. C., Homan, K. J., Williams, S. E., King, C. D. 2021; 37 (6): 443-453

  Abstract

  Intensive interdisciplinary pain treatment (IIPT) programs have been shown to restore function, improve coping, and reduce pain in adolescents with chronic pain. Yet, little is known about patients' sleep during IIPT and whether or not improvements in pain treatment outcomes are associated with changes in sleep pre-to-post IIPT treatment. The objectives of the current study were to describe sleep among adolescents entering IIPT and examine associations between sleep parameters and IIPT treatment effects.Self-reported sleep measures and clinical outcomes (eg, functional disability, coping, average pain), were collected from 44 adolescents (mean age=14.57, 68.2% female) at admission and discharge from an inpatient IIPT program. Wrist-worn actigraphy data and sleep diaries from participants' first week and last week in the program were analyzed to characterize sleep parameters.Participants self-reported poor sleep/wake patterns, high levels of insomnia symptoms, and subclinical problems with daytime sleepiness upon admission into IIPT, although actigraphic indices of sleep from the first week of IIPT admission were only just under clinical guidelines for healthy adolescent sleep. Better self-reported sleep quality assessed via aggregated sleep diaries from the first week was associated with improvement in average pain and disability over the course of the program. Furthermore, improvements in insomnia symptoms and daytime sleepiness throughout the program were positively correlated with concurrent improvements in functional disability and coping.Taken together, results suggest that sleep may be associated with IIPT treatment effects and pave the way for future research to continue examining these relationships.

  View details for DOI 10.1097/AJP.0000000000000936

  View details for Web of Science ID 000656197400007

  View details for PubMedID 33782245

  View details for PubMedCentralID PMC8102426

• A novel behavioral health program for family caregivers of children admitted to a transitional chronic ventilator unit PEDIATRIC PULMONOLOGY Borschuk, A. P., Williams, S. E., McClure, J. M., Kendall, M., Mack, L., Coleman, M., Gurbani, N., Benscoter, D., Amin, R., Stark, L. J. 2021; 56 (6): 1635-1643

  Abstract

  The care of mechanically ventilated pediatric patients is complex and burdensome. It is essential to adequately support the family caregivers of these children to optimize outcomes; however, there is no literature describing interventions for caregivers in this population.This study described a novel behavioral health program and examined its impact on family caregiver engagement and psychological distress on a pediatric inpatient chronic ventilator unit.Electronic chart review was completed with retrospective and prospective participant enrollment for the purposes of longitudinal evaluation of caregiver engagement. For analytic purposes, participants were grouped into three categories: (1) preprogram, (2) postprogram, and (3) postprogram with completion of psychotherapy.The behavioral health program was associated with increased caregiver participation in rounds, t = 7.76, p = < .001. Parents who completed a course of psychotherapy within the behavioral health program demonstrated reduced time to training completion (F = 5.89; p < .01), higher staff-rated caregiver engagement (F = 3.69; p < .05), and significantly reduced levels of caregiver distress (t = 2.09; p < .05).

  View details for DOI 10.1002/ppul.25327

  View details for Web of Science ID 000623511800001

  View details for PubMedID 33647193

• Randomized clinical trial of Fibromyalgia Integrative Training (FIT teens) for adolescents with juvenile fibromyalgia ? Study design and protocol CONTEMPORARY CLINICAL TRIALS Kashikar-Zuck, S., Briggs, M. S., Bout-Tabaku, S., Connelly, M., Daffin, M., Guite, J., Ittenbach, R., Logan, D. E., Lynch-Jordan, A. M., Myer, G. D., Ounpuu, S., Peugh, J., Schikler, K., Sugimoto, D., Stinson, J. N., Ting, T., Thomas, S., Williams, S. E., Zempsky, W., Childhood Arthrit Rheumatology Res 2021; 103: 106321

  Abstract

  Juvenile-onset fibromyalgia (JFM) is a chronic debilitating pain condition that negatively impacts physical, social and academic functioning. Cognitive-behavioral therapy (CBT) is beneficial in reducing functional disability among adolescents with JFM but has only a modest impact on pain reduction and does not improve physical exercise participation. This randomized controlled trial (RCT) aims to test whether a novel intervention that combines CBT with specialized neuromuscular exercise training (the Fibromyalgia Integrative Training program for Teens "FIT Teens") is superior to CBT alone or a graded aerobic exercise (GAE) program.This 3-arm multi-site RCT will examine the efficacy of the FIT Teens intervention in reducing functional disability (primary outcome) and pain intensity (secondary outcome), relative to CBT or GAE. All interventions are 8-weeks (16 sessions) in duration and are delivered in small groups of 4-6 adolescents with JFM. A total of 420 participants are anticipated to be enrolled across seven sites with approximately equal allocation to each treatment arm. Functional disability and average pain intensity in the past week will be assessed at baseline, post-treatment and at 3-, 6-, 9- and 12-month follow-up. The 3-month follow-up is the primary endpoint to evaluate treatment efficacy; longitudinal assessments will determine maintenance of treatment gains. Changes in coping, fear of movement, biomechanical changes and physical fitness will also be evaluated.This multi-site RCT is designed to evaluate whether the combined FIT Teens intervention will have significantly greater effects on disability and pain reduction than CBT or GAE alone for youth with JFM. Clinical trials.gov registration: NCT03268421.

  View details for DOI 10.1016/j.cct.2021.106321

  View details for Web of Science ID 000645089200004

  View details for PubMedID 33618033

  View details for PubMedCentralID PMC8089039

• Leveraging VR/AR to combat chronic pain in youth: Position paper from the Interdisciplinary Network on Virtual and Augmented (AR/VR) Technologies for Pain (INOVATE-Pain) Management. Journal of medical Internet research Logan, D. E., Simons, L. E., Caruso, T. n., Gold, J. I., Greenleaf, W. n., Griffin, A. n., King, C. n., Menendez, M. n., Olbrecht, V. n., Rodriguez, S. n., Silvia, M. n., Stinson, J. n., Wang, E. n., Williams, S. n., Wilson, L. n. 2021

  Abstract

  Virtual reality (VR) and augmented reality (AR) interventions are emerging as promising tools in the treatment of pediatric chronic pain conditions, but in this young field there is little consensus to guide the process of engaging in the development and evaluation of targeted VR-based interventions.The INOVATE-Pain consortium aims to advance the field of VR for pediatric chronic pain rehabilitation by providing guidance for best practices in the design, evaluation, and dissemination of VR-based interventions targeting this population.An interdisciplinary meeting of 16 academics, clinicians, industry and philanthropy partners was held in January 2020.Reviewing the state of the field, the consortium identified important directions for research-driven innovation in VR/AR clinical care, highlighted key opportunities and challenges facing the field, and established a consensus on best methodological practices to adopt in future efforts to advance the research and practice of VR/AR in pediatric pain. The consortium also identified important next steps to undertake to continue to advance the work in this promising new area of digital health pain interventions.To realize the promise of this realm of innovation, key ingredients for the success include productive partnerships among industry, academic, and clinical stakeholders, a uniform set of outcome domains and measures for standardized evaluation, and widespread access to the latest opportunities, tools and resources. The INOVATE-Pain collaborative hopes to promote the creation, rigorous yet efficient evaluation, and dissemination of innovative VR-based interventions to reduce pain and improve quality of life for children.

  View details for DOI 10.2196/25916

  View details for PubMedID 33667177

• Sleep among Youth with Severely Disabling Chronic Pain: Before, during, and after Inpatient Intensive Interdisciplinary Pain Treatment CHILDREN-BASEL Krietsch, K. N., Beebe, D. W., King, C., Homan, K. J., Williams, S. E. 2021; 8 (1)

  Abstract

  Poor sleep is commonly reported in pediatric chronic pain. There are signals that intensive interdisciplinary pain treatments (IIPT) may inadvertently improve objective sleep, but this claim cannot be substantiated without baseline sleep data prior to IIPT. This study followed the objective sleep/wake patterns (e.g., duration, quality, timing, consistency) of pediatric patients with severely functionally disabling chronic pain before, during, and after inpatient IIPT (the Functional Independence Restoration Program-"FIRST Program"), alongside a similarly-disabled chronic pain Comparison Group. The final sample included N = 10 FIRST Patients and N = 9 Comparison Group patients. At baseline, the whole sample showed healthy sleep duration (~9 h), average sleep efficiency <90%, late sleep onset and offset (mean = 11:56 p.m.-8:50 a.m.), and highly inconsistent sleep schedules night to night. During IIPT, FIRST Patients maintained healthy sleep durations, moved sleep schedules 2 h earlier, and decreased timing and duration variability by >60 min while the Comparison Group maintained similar sleep to baseline. At follow up (1-2 months later), FIRST Patients' sleep schedules shifted later but were still less variable than at baseline. Results point to the malleability of sleep/wake patterns within treatment contexts with strict environmental control but suggest that these gains may be difficult for youth with chronic pain to maintain in the home environment.

  View details for DOI 10.3390/children8010042

  View details for Web of Science ID 000610010700001

  View details for PubMedID 33445734

  View details for PubMedCentralID PMC7828171

• Dream It! Preliminary Evidence for an Educational Tool to Increase Children's Optimistic Thinking CHILD & YOUTH CARE FORUM Jacquez, F., Trott, C. D., Wren, A. R., Ashraf, L. J., Williams, S. E. 2020; 49 (6): 877-892

  View details for DOI 10.1007/s10566-020-09561-6

  View details for Web of Science ID 000547347300001

• The role of pain rehabilitation in an adolescent sickle cell disease population: a case series PEDIATRIC HEMATOLOGY AND ONCOLOGY Collins, A. B., McTate-Acosta, E. A., Williams, S. E. 2020; 37 (7): 637-644

  View details for DOI 10.1080/08880018.2020.1762811

  View details for Web of Science ID 000534509200001

  View details for PubMedID 32401110

• Parent Attributions of Ambiguous Symptoms in Their Children: A Preliminary Measure Validation in Parents of Children with Chronic Pain CHILDREN-BASEL Heathcote, L. C., Williams, S. E., Smith, A. M., Sieberg, C. B., Simons, L. E. 2018; 5 (6)

  View details for DOI 10.3390/children5060076

  View details for Web of Science ID 000436273300013