Examining predictors of treatment effect in digital Acceptance and Commitment Therapy for chronic pain.

Digitally delivered behavioral interventions for chronic pain have been encouraging with effects similar to face-to-face treatment. Although many chronic pain patients benefit from behavioral treatment, a substantial proportion do not improve. To contribute to more knowledge about factors that predict treatment effects in digitally delivered behavioral interventions for chronic pain, the present study analyzed pooled data (N = 130) from three different studies on digitally delivered Acceptance and Commitment Therapy (ACT) for chronic pain. Longitudinal linear mixed-effects models for repeated measures were used to identify variables with significant influence on the rate of improvement in the main treatment outcome pain interference from pre- to post-treatment. The variables were sorted into six domains (demographics, pain variables, psychological flexibility, baseline severity, comorbid symptoms and early adherence) and analysed in a stepwise manner. The study found that shorter pain duration and higher degree of insomnia symptoms at baseline predicted larger treatment effects. The original trials from which data was pooled are registered at clinicaltrials.gov (registration number: NCT03105908 and NCT03344926).

ACTsmart: Guided Smartphone-Delivered Acceptance and Commitment Therapy for Chronic Pain-A Pilot Trial.

BACKGROUND: Acceptance and commitment therapy (ACT) is a behavioral health intervention with strong empirical support for chronic pain but, to date, widespread dissemination is limited. Digital solutions improve access to care and can be integrated into patients' everyday lives. OBJECTIVE: ACTsmart, a guided smartphone-delivered ACT intervention, was developed to improve the accessibility of an evidence-based behavioral treatment for chronic pain. In the present study, we evaluated the preliminary efficacy of ACTsmart in adults with chronic pain. METHODS: The study was an open-label pilot trial. The treatment lasted for 8 weeks, and participants completed all outcome measures at pretreatment and posttreatment and at 3-, 6-, and 12-month follow-ups, with weekly assessments of selected measures during treatment. The primary outcome was pain interference. The secondary outcomes were psychological flexibility, values, insomnia, anxiety, depressive symptoms, health-related quality of life, and pain intensity. All outcomes were analyzed using linear mixed-effects models. RESULTS: The sample consisted of 34 adults (88% women) with long-standing chronic pain (M=20.4 years, SD=11.7). Compliance to treatment was high, and at the end of treatment, we observed a significant improvement in the primary outcome of pain interference (d = -1.01). All secondary outcomes significantly improved from pretreatment to posttreatment with small to large effect sizes. Improvements were maintained throughout 12 months of follow-up. CONCLUSION: The results of this pilot study provide preliminary support for ACTsmart as an accessible and effective behavioral health treatment for adults with chronic pain and warrant a randomized controlled trial to further evaluate the efficacy of the intervention.

Internet-Delivered Acceptance and Commitment Therapy for Adolescents with Chronic Pain and Their Parents: A Nonrandomized Pilot Trial.

BACKGROUND: Acceptance and Commitment Therapy (ACT) is an empirically supported treatment for chronic pain in adults. There is also a small but growing evidence base of ACT for pediatric chronic pain. However, because of limited access to psychological treatment for pain, and geographical distances from pain facilities, many patients will not receive such treatment. OBJECTIVE: The aim of the study was to evaluate the feasibility and preliminary effects of an internet-delivered ACT for adolescents with chronic pain, and their parents. METHODS: In this nonrandomized pilot study 28 self-recruited adolescents, aged 13-17 years, received 8 weeks of internet-delivered ACT, while outcomes were assessed at pre-, posttreatment, and at follow-up (17-25 weeks). Parents of the adolescents received an 8-week internet-delivered parental program, and their outcomes were assessed at the same timepoints. Both treatments were guided by a therapist experienced in ACT and chronic pain. RESULTS: Some threats to feasibility were identified such as slow recruitment rate, low compliance and a delay in completion of follow-up assessments. Preliminary outcome evaluation showed that adolescents showed a large significant improvement on their main outcome (pain interference, d = 1.09), and parents a medium improvement on their main outcome, pain reactivity (d = 0.70). Improvements were also seen in adolescents' depressive symptoms and insomnia severity. CONCLUSION: The preliminary results of internet-delivered ACT are promising with regards to improvements in adolescent and parent outcome. Measures to improve feasibility are needed prior to conducting a larger randomized trial.

Feasibility of group-based acceptance and commitment therapy for adolescents (AHEAD) with multiple functional somatic syndromes: a pilot study.

BACKGROUND: Recurrent and impairing functional somatic syndromes (FSS) are common in adolescents. Despite a high need for care, empirically supported treatments are lacking for youth. The aim of this uncontrolled pilot study was to assess feasibility and treatment potential of a new intervention with group-based Acceptance and Commitment Therapy (ACT) in a generic treatment approach for adolescents with multiple FSS. METHODS: Twenty-one patients received 'ACT for Health in Adolescents' (AHEAD) (30 h), specifically developed for adolescents (aged 15-19 years) with moderate to severe FSS. Close relatives attended an information meeting to facilitate support of the patients throughout treatment. Treatment satisfaction was evaluated by means of self-report and relatives' impressions. Self-reported physical health at 3 months follow-up (FU) after end of treatment was the primary outcome whereas secondary outcomes included symptom burden, limitation due to symptoms, illness worry, emotional distress and physical and emotional symptoms. Treatment targets were assessed by measures on illness behaviour, illness perception and psychological inflexibility. RESULTS: Nineteen patients (90.5%) completed the treatment with a high overall attendance rate of 93%. All would recommend the treatment to a friend with similar problems. Close relatives rated it valuable to participate in an information meeting. Patients' physical health improved significantly from assessment to FU with a clinically relevant mean change of 8.9 points (95% CI [5.4; 12.4]; SRM 0.91 [0.26;1.57]). Improvement was also seen on all secondary outcome measures, from assessment to FU. Maladaptive illness behaviours and perceptions as well as psychological inflexibility showed a significant decline from assessment to FU. CONCLUSION: AHEAD was feasible and potentially efficacious and warrants testing in a larger clinical trial. TRIAL REGISTRATION: Clinical Trials gov NCT04464447 , registration date July 9th, 2020. Retrospectively registered.

A case report and literature review of autism and attention deficit hyperactivity disorder in paediatric chronic pain.

Psychiatric disorders are common in paediatric patients with chronic pain, but the overall prevalence of comorbid neurodevelopmental disorders is unclear. We report on a case of severe chronic pain in a child with undiagnosed comorbid autism spectrum disorder and attention deficit hyperactivity disorder, where significant improvements in pain and function occurred following methylphenidate medication and parental behavioural training. CONCLUSION: The inclusion of behavioural assessment and screening for neurodevelopmental comorbidity may be essential in addressing complex paediatric chronic pain.

Analyzing Change Processes Resulting from a Smartphone Maintenance Intervention Based on Acceptance and Commitment Therapy for Women with Chronic Widespread Pain.

PURPOSE: This study investigated change processes resulting from a randomized controlled trial smartphone-delivered maintenance intervention with daily electronic diaries and personalized written feedback based on acceptance and commitment therapy (ACT) following a rehabilitation program for patients with chronic widespread pain. METHOD: This study included 48 women who during a 5-week period completed electronic diaries three times daily, totaling 3372 entries. In response to the completed diaries, they received daily feedback from a therapist for 4 weeks (excluding weekends), totaling 799 feedback messages. To analyze the change processes, we explored the associations between feedback and daily ratings of participants' physical activities, positive emotions, pain fear and avoidance, pain acceptance, and self-management. Commitment to physical activities and the participants' evaluation of feedback were also analyzed. Multilevel models were used in the statistical analyses. RESULTS: Participants' average pain fear and avoidance decreased over the intervention period (mean -0.019, P = 0.05). Self-management, pain acceptance, and positive feelings increased (mean -0.030, P < 0.01; mean -0.015, P < 0.01; and mean -0.011, P = 0.01, respectively). Participants' performance of physical activities decreased slightly over time, but the level of commitment was high and they evaluated the feedback as supportive for staying sufficiently active. No correlation between diary contents and feedback messages was found, even though most of the participants evaluated the feedback as supportive. CONCLUSION: No support was found for an association between diary content and feedback based on ACT. However, diary measures were consistent with the ACT model and may have influenced positively the change processes.

Low-grade inflammation may moderate the effect of behavioral treatment for chronic pain in adults.

The purpose of the present pilot study was to explore the moderating role of basal inflammation on the effects of behavioral pain treatment in 41 patients with long-standing pain. Baseline pro-inflammatory status moderated behavioral treatment outcomes: higher pre-treatment levels of Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-6 were related to less improvement in pain intensity, psychological inflexibility and in mental health-related quality of life. The treatment outcomes improved in the subgroup that had low levels of pro-inflammatory cytokines at baseline, while the subjects with higher pro-inflammatory status did not. Altogether, results indicate that low-grade inflammation may influence the behavioral treatment outcomes and provide a possible explanation of the heterogeneity in treatment response.

Development and validation of the English Pain Interference Index and Pain Interference Index-Parent report.

OBJECTIVE: Measurement of pain interference in children is challenged by a lack of validated measures with a parent proxy report. This study investigated the psychometric properties of the Pain Interference Index (PII), a six-item questionnaire originally developed in Swedish, in chronically ill youth. METHODS: We adapted the PII for English-speaking participants and created a parallel parent proxy measure. Respondents indicate how much pain has interfered with the child's life in the past 2 weeks (0-6 scale); higher scores indicate more pain interference. Eligible participants included individuals 6-25 years with neurofibromatosis type 1 (NF1) and cancer. Internal consistency was assessed; validity was examined by correlating PII scores with existing measures of pain interference (Modified Brief Pain Inventory [MBPI]) and pain intensity (visual analogue scale [VAS]), and with measures of disease severity. RESULTS: Among 60 participants (mean age 14.7 years, range 6-24) and their parents, PII internal consistency was 0.84 and 0.96, respectively. PII scores correlated with MBPI (r = 0.81, P < 0.0001) and VAS (r = 0.55, P < 0.0001) scores and differentiated between patients with mild vs moderate/severe NF1 disease severity (P < 0.05). The PII-Parent was significantly correlated with the mothers' and fathers' VAS rating of the child's pain intensity (Ps < 0.01). CONCLUSIONS: Internal consistency of the English PII is high; validity is supported by the PII's correlations with other measures of pain interference and pain intensity, and with disease severity in patients with NF1. Preliminary data indicate that the English PII is a reliable, valid, feasible pain interference measure for youth with NF1 and cancer.

Internet-delivered acceptance and values-based exposure treatment for fibromyalgia: a pilot study.

BACKGROUND: Acceptance and commitment therapy (ACT) is a promising treatment option for fibromyalgia (FM). Studies have shown that many cognitive behavioral protocols can be transferred to the Internet with sustained efficacy. However, no study has investigated the effect on an Internet-delivered ACT-based protocol for FM. This study evaluated the efficacy, acceptability, and the health economic effects of an Internet-delivered acceptance and values-based exposure treatment for FM. METHODS: This open pilot trial included 41 self-referred women with a FM diagnosis. The 10-week Internet-delivered treatment included acceptance, mindfulness, work with life-values, and systematic exposure to FM symptoms and FM-related situations. Participants also had regular contact with an assigned online therapist. Assessments were made at pretreatment, post-treatment, and 6-month follow-up. RESULTS: The treatment was completed by 70% of the participants. Attrition rates were low, with 98% completing the post-treatment assessment and 90% completing the 6-month follow-up assessment. Multiple imputations were used to replace missing values. Pre- to post-treatment within-group effect sizes were in the moderate to large range (Cohen's d = 0.62-1.56) on measures of FM symptoms and impact, disability, quality of life, depression, anxiety, fatigue, and psychological flexibility. All improvements were maintained at follow-up. Economical analyses revealed significant societal cost reductions that offset the treatment costs within 2 months of treatment completion. CONCLUSIONS: An Internet-delivered psychological treatment based on acceptance and exposure principles seems to be an efficacious, acceptable, and cost-effective treatment for FM. Randomized controlled trials are needed to confirm these results.

Associations between sickness behavior, but not inflammatory cytokines, and psychiatric comorbidity in chronic pain.

OBJECTIVES: Approximately one in five adults experiences chronic pain, often in co-occurrence with depression, insomnia, anxiety, and lower self-rated health. Elevated levels of cytokines, e.g. tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10), have been identified in patients with chronic pain. Depression, insufficient sleep, poor self-rated health, and pain intensity have also been associated with inflammatory biomarkers. This study aimed to investigate the interrelationships between inflammatory biomarkers and depression, insomnia, anxiety, self-rated health, sickness behavior, and pain intensity in patients with chronic pain. METHODS: Self-report questionnaires and blood samples analyzed for plasma levels of inflammatory biomarkers were collected from 80 adult patients with chronic pain. Associations between inflammatory biomarkers (TNF-α, IL-6, IL-8, IL-10, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) and depression, insomnia, anxiety, self-rated health, sickness behavior, and pain intensity, were analyzed using bivariate Spearman rank correlation coefficients and regression analyses. RESULTS: Participants were mainly women (72.5 %), with a mean age of 50.8 years, and a reported mean pain duration of 16.7 years. There were significant correlations between insomnia and CRP (rs =.26, p <.05); sex and ESR (rs =.29, p <.05); age and IL-6 (rs =.29, p <.05) and IL-8 (rs =.30, p <.05); BMI and IL-6 (rs =.50, p <.001), CRP (rs =.63, p <.001) and ESR (rs =.42, p <.001). Ratings of depression were positively and significantly related to ratings of sickness behavior and anxiety (ß =.32 and ß =.40, respectively), explaining 49 % of the total variance in depression ratings. Insomnia was positively and significantly related to sickness behavior (ß =.37) explaining 31 % of the total variance in insomnia ratings. Inflammatory biomarkers, however, did not contribute significantly to the models. CONCLUSIONS: Participants reported high levels of symptoms, yet the associations between these ratings and the inflammatory biomarkers were either absent or weak. Also, despite high levels of self-reported sickness behavior, overall the inflammatory status remained within the normal range. Ratings of sickness behavior contributed more than inflammatory markers in explaining ratings of depression and insomnia. The present results point to the complexity of chronic pain, and the challenges of identifying biomarkers that explain symptomatology.

Child and Parent Risk and Resilience Factors as Predictors of Long-term Recovery in Youth Undergoing Spinal Fusion Surgery.

OBJECTIVES: Undertreated pediatric postsurgical pain negatively affects health-related quality of life (HRQOL) and functioning and may lead to chronic postsurgical pain (CPSP). Predictors of recovery have been identified but more research is needed, particularly regarding resilience, social factors, and long-term effects. The aim of the present study was to investigate child and parent risk and resilience factors as predictors of long-term postsurgical recovery for adolescents. METHODS: Participants were patients with Adolescent Idiopathic Scoliosis (AIS), 12 to 18 years old, undergoing spinal fusion, and their parents. Recruitment occurred at the orthopedic units at 4 hospitals in Belgium. Data were collected before surgery (T0), at 3 (T1) and 6 weeks (T2), 6 months (T3), and 1 year (T4) post surgery. Multiple regression models were used to evaluate the predictive effect of pain intensity, pain catastrophizing, psychological flexibility, and pain acceptance on long-term functioning, HRQOL, and pain. RESULTS: The sample comprised 100 adolescents and 61 parents. Pain at T0, T1, and T3 and adolescent pain catastrophizing (T0) predicted health-related quality of life, functioning, and pain at T4 (while pain at T2 predicted HRQOL and pain). Parent pain catastrophizing predicted pain at T4. Adolescent and parental psychological flexibility predicted HRQOL, and parent psychological flexibility also predicted pain at T4. Adolescent acceptance at T1 predicted pain, and acceptance at T2 predicted HRQOL, at T4. DISCUSSION: The study identified pain and adolescent pain catastrophizing as risk factors, and adolescent and parental psychological flexibility and adolescent pain acceptance as resilience factors, for long-term recovery in youths undergoing spinal fusion. Postsurgical pain management targeting these factors may therefore promote recovery for these adolescents.

A randomized controlled trial of graded exposure treatment (GET living) for adolescents with chronic pain.

ABSTRACT: Graded exposure treatment (GET) is a theory-driven pain treatment that aims to improve functioning by exposing patients to activities previously feared and avoided. Combining key elements of GET with acceptance-based exposure, GET Living (GL) was developed for adolescents with chronic pain (GL). Based on robust treatment effects observed in our single-case experimental design pilot trial of GL (NCT01974791), we conducted a 2-arm randomized clinical trial comparing GL with multidisciplinary pain management (MPM) comprised of cognitive behavioral therapy and physical therapy for pain management (NCT03699007). A cohort of 68 youth with chronic musculoskeletal pain (M age 14.2 years; 81% female) were randomized to GL or MPM. Owing to COVID-19 restrictions, 54% of participants received zoom video delivered care. Assessments were collected at baseline, discharge, as well as at 3-month and 6-month follow-up. Primary outcomes were self-reported pain-related fear and avoidance. Secondary outcomes were child functional disability and parent protective responses to child pain. As hypothesized, GL improved in primary and secondary outcomes at 3-month follow-up. Contrary to our superiority hypothesis, there was no significant difference between GL and MPM. Patients reported both GL and MPM (in person and video) as credible and were highly satisfied with the treatment experience. Next steps will involve examining the single-case experimental design data embedded in this trial to facilitate an understanding of individual differences in treatment responses (eg, when effects occurred, what processes changed during treatment within the treatment arm). The current findings support GET Living and MPM for youth with chronic pain.

Internet-delivered cognitive behavioral therapy for adolescents with insomnia: Feasibility and preliminary efficacy.

BACKGROUND: Insomnia is common in adolescents. This study evaluated feasibility and preliminary efficacy of a six-week internet-delivered cognitive-behavioral therapy for insomnia (ICBT-I) in adolescents. METHODS: In this uncontrolled pilot study, participants (n = 27, 78% female) completed assessments pre- and post intervention. Data on recruitment, adherence to treatment, treatment activity, satisfaction and credibility was collected to assess feasibility. Self-reported insomnia symptoms, sleep parameters as well as depression, anxiety and daytime function were also assessed. RESULTS: Participants showed good adherence to treatment and found the intervention overall credible and satisfactory. From pre- to post-assessment, statistically significant improvements were found for insomnia symptoms (p < .001; d = 1.02), sleep onset latency (p < .001; d = .39), wake after sleep onset (p = .001; d = .34), sleep efficiency (p < .001; d = .5) and depression (p = .01, d = .37). Changes in scores of total sleep time, generalized anxiety, daytime sleepiness and functional disability were not significant. CONCLUSIONS: The present study indicates that ICBT-I is well accepted by adolescents, that insomnia symptoms and sleep parameters can improve following the intervention, and that co-morbid symptoms of depression can be reduced. Due to the limited sample size and the uncontrolled design, the suggested results need to be replicated in well-powered controlled clinical trials.

Inflammatory Blood Signature Related to Common Psychological Comorbidity in Chronic Pain.

Chronic pain is characterized by high psychological comorbidity, and diagnoses are symptom-based due to a lack of clear pathophysiological factors and valid biomarkers. We investigate if inflammatory blood biomarker signatures are associated with pain intensity and psychological comorbidity in a mixed chronic pain population. Eighty-one patients (72% women) with chronic pain (>6 months) were included. Patient reported outcomes were collected, and blood was analyzed with the Proseek Multiplex Olink Inflammation Panel (Bioscience Uppsala, Uppsala, Sweden), resulting in 77 inflammatory markers included for multivariate data analysis. Three subgroups of chronic pain patients were identified using an unsupervised principal component analysis. No difference between the subgroups was seen in pain intensity, but differences were seen in mental health and inflammatory profiles. Ten inflammatory proteins were significantly associated with anxiety and depression (using the Generalized Anxiety Disorder 7-item scale (GAD-7) and the Patient Health Questionnaire (PHQ-9): STAMBP, SIRT2, AXIN1, CASP-8, ADA, IL-7, CD40, CXCL1, CXCL5, and CD244. No markers were related to pain intensity. Fifteen proteins could differentiate between patients with moderate/high (GAD-7/PHQ-9 > 10) or mild/no (GAD-7/PHQ-9 < 10) psychological comorbidity. This study further contributes to the increasing knowledge of the importance of inflammation in chronic pain conditions and indicates that specific inflammatory proteins may be related to psychological comorbidity.

Pain acceptance and psychological inflexibility predict pain interference outcomes for persons with chronic pain receiving pain psychology.

OBJECTIVES: Awareness (being present), acceptance, and engagement (committed action) are three dimensions of psychological flexibility. Understanding these in the context of chronic pain may identify treatment targets to help refine individual treatment. Our objective was to test the predictive capacity of three dimensions within the psychological flexibility model on the longitudinal trajectory of pain interference. METHODS: Patients receiving pain psychology treatment at a pain management center participated in this pragmatic clinical longitudinal study (n=86 with at least three assessments; Mean age=51 years; Gender=60 females, 26 males). Measures included the Five Facet Mindfulness Questionnaire (FFMQ-SF); Chronic Pain Acceptance Questionnaire (CPAQ-8); Psychological Inflexibility in Pain Scale (PIPS-12); and Committed Action Questionnaire (CAQ-8). The dependent variable was the Patient Reported Outcomes Information System (PROMIS) Pain Interference (PI). We used latent growth modelling to analyze scores assessed within 180 days of patient care. RESULTS: Psychological inflexibility (PIPS-12) and pain acceptance (CPAQ-8) measured at baseline predicted PI outcomes (n=86). PIPS-12 showed a direct relationship with pain interference (PI), where higher PIPS-12 scores predicted significantly higher PI mean scores on average across the study period (ρ=0.422, r2=0.382) but also predicted significantly greater decreases in PI across time (ρ=-0.489, r2=0.123). Higher CPAQ-8 scores predicted significantly lower PI mean scores on average across the study period (ρ=-0.478, r2=0.453) but also significantly smaller decreases in PI across time (ρ=0.495, r2=0.076). Awareness (FFMQ-SF) and engagement (CAQ-8) were not predictive of PI outcomes. CONCLUSIONS: Patients who entered pain psychology treatment with lower pain acceptance and higher psychological inflexibility showed the largest reductions in pain interference across time. These results contribute towards a novel prognostic understanding of the predictive roles of an enhancing dimension and limiting dimension of psychological flexibility.

Using Personas in the development of eHealth interventions for chronic pain: A scoping review and narrative synthesis.

Objectives: Behavioral eHealth interventions can enhance self-management and improve well-being in people with chronic pain. The development of these interventions calls for a user-centered approach to ensure that patient needs are appreciated. However, it may be challenging to involve patients; particularly during the early stages of the process. Fictional user profiles, known as Personas, can represent needs and guide designing eHealth interventions. This article provides a comprehensive overview of the use of Personas in the development of behavioral eHealth interventions for people with chronic pain with the aim to identify benefits and challenges. Methods: Bibliographic databases (Medline, Web of Science Core Collection, PsycInfo, CINAHL) and registries (PubMed Central, medaRxiv) were systematically searched. In a double-reviewing process, n = 6830 hits and n = 351 full-texts were screened and read. Ten peer-reviewed studies published between 2017 and 2022 were included in the narrative synthesis. Findings: Ten studies reported using "Pain Personas" in the development of eHealth interventions for such purposes as to gain a shared understanding of the user and to discuss solutions in team meetings, or for patients to identify with (if Personas are included in the intervention). Personas were based on qualitative and/or quantitative data. However, the procedure for creating Personas was only described in half of the included studies (n = 5). These five studies provided descriptive details of the Personas (i.e., picture, name, narrative of their pain behavior, technological skills, and motivation). Conclusions: Although Personas have been used by pain researchers in recent projects and were highlighted as an important ingredient in the development process, available design guidelines for the creation and use of Personas are not followed or communicated transparently. Benefits and challenges when using Personas in the development of eHealth interventions for people with chronic pain are discussed to support future eHealth efforts and to improve the quality of eHealth innovation in the field of pain.

Protocol for a multi-phase, multi-center, real-world, hybrid effectiveness-implementation study of a digital intervention for pediatric chronic pain co-designed with patients (Digital SPA).

Background: Children and adolescents with chronic pain are a vulnerable population who often lack the resources to manage their condition. Due to high personal, social, and economic consequences, proper management in its early stages is key to reducing disability. The aim of this project is to co-develop a digital intervention for pediatric chronic pain (Digital SPA) with end-users and to evaluate its effectiveness and implementation outcomes in Spain. Methods: (Phase 1) Focus groups with patients, parents, and clinicians (n = 5-6 each) will inform about unmet pain care needs and provide a starting point for co-designing the intervention. (Phase 2) Content creation and usability testing will be based on the results of Phase 1, and the theory-driven development will follow the latest available evidence. The intervention will use validated psychological techniques focused on improving functioning by teaching pain coping skills. (Phase 3) Hybrid effectiveness-implementation trial. Participants (n = 195) will be adolescents aged 12-17 years old with chronic pain and one of their parents. Assessments include physical function, pain, sleep, anxiety, mood, satisfaction and adherence to the treatment, and number of visits to the emergency room. A qualitative framework analysis will be conducted with data from Phase 1. Effects of the intervention will be evaluated using linear multilevel modeling. The Consolidated Framework for Implementation Research (CFIR) and Behavioral Interventions Using Technology (BIT) frameworks will be used to evaluate implementation. Discussion: This study is expected to produce a co-created evidence-based digital intervention for pediatric chronic pain and a roadmap for successful implementation. Trial registration number TRN and date of registration: ClinicalTrials.gov (registered on 26 June 2023: https://clinicaltrials.gov/study/NCT05917626). Contributions to the literature The implementation of digital health interventions has two major gaps: (1) adherence to treatment is suboptimal, and (2) the process of making the interventions available to the end-user in a sustainable way is often unsuccessful.In this study, we expect that assessing users' needs and co-designing an intervention with them will improve adherence.Documenting the implementation process from the project inception and integrating the results into an implementation framework will allow for replication and extension in different contexts.This study will increase the knowledge about implementation in a vulnerable population: adolescents with chronic pain without access to in-person multidisciplinary pain care.

Baseline Pro-Inflammatory Cytokine Levels Moderate Psychological Inflexibility in Behavioral Treatment for Chronic Pain.

Background: The medical and scientific communities struggle to understand chronic pain and find effective treatments. Multimodal approaches are encouraging but show significant individual differences. Methods: Seventy-eight persons (56 women) with chronic pain received Acceptance and Commitment Therapy and provided blood samples before and after treatment. The participants completed surveys with the blood sampling. Blood plasma was analyzed for IL-6 and TNF-α levels with the Olink Inflammation Panel (Olink Bioscience Uppsala, Sweden). The treatment effects and moderating effects of low-grade inflammation on changes in outcomes were analyzed using linear mixed models. Results: Pain interference (p < 0.001) and psychological inflexibility (p < 0.001) improved significantly during treatment, but pain intensity did not (p = 0.078). Cytokine levels did not change over the course of the treatment (IL-6/TNF-α p = 0.086/0.672). Mean baseline levels of IL-6 and TNF-α moderated improvement in psychological inflexibility during the course of treatment (p = 0.044), but cytokine levels did not moderate changes in pain interference (p = 0.205) or pain intensity (p = 0.536). Conclusions: Higher baseline inflammation levels were related to less improvement in psychological inflexibility. Low-grade inflammation may be one factor underlying the variability in behavioral treatment in chronic pain.

Development, evaluation and implementation of a digital behavioural health treatment for chronic pain: study protocol of the multiphase DAHLIA project.

INTRODUCTION: Chronic pain affects about 20%-40% of the population and is linked to mental health outcomes and impaired daily functioning. Pharmacological interventions are commonly insufficient for producing relief and recovery of functioning. Behavioural health treatment is key to generate lasting benefits across outcome domains. However, most people with chronic pain cannot easily access evidence-based behavioural interventions. The overall aim of the DAHLIA project is to develop, evaluate and implement a widely accessible digital behavioural health treatment to improve well-being in individuals with chronic pain. METHODS AND ANALYSIS: The project follows the four phases of the mHealth Agile Development and Evaluation Lifecycle: (1) development and pre-implementation surveillance using focus groups, stakeholder interviews and a business model; (2) iterative optimisation studies applying single case experimental design (SCED) method in 4-6 iterations with n=10 patients and their healthcare professionals per iteration; (3) a two-armed clinical randomised controlled trial enhanced with SCED (n=180 patients per arm) and (4) interview-based post-market surveillance. Data analyses include multilevel modelling, cost-utility and indicative analyses.In October 2021, inter-sectorial partners are engaged and funding is secured for four years. The treatment content is compiled and the first treatment prototype is in preparation. Clinical sites in three Swedish regions are informed and recruitment for phase 1 will start in autumn 2021. To facilitate long-term impact and accessibility, the treatment will be integrated into a Swedish health platform (www.1177.se), which is used on a national level as a hub for advice, information, guidance and e-services for health and healthcare. ETHICS AND DISSEMINATION: The study plan has been reviewed and approved by Swedish ethical review authorities. Findings will be actively disseminated through peer-reviewed journals, conference presentations, social media and outreach activities for the wider public. TRIAL REGISTRATION NUMBER: NCT05066087.

Agile development of a digital exposure treatment for youth with chronic musculoskeletal pain: protocol of a user-centred design approach and examination of feasibility and preliminary efficacy.

INTRODUCTION: Chronic pain affects a significant number of children and impacts multiple domains including social, emotional and behavioural functioning, and negatively impacts family functioning. Roughly 5% of youth with chronic pain experience moderate to severe pain-related disability, with pain-related fear and avoidance of activities being identified as substantial barriers to treatment engagement. Evidence supports targeted psychological and physical interventions to address these barriers (eg, graded-exposure treatment), but accessibility to intervention is undermined by a shortage of services outside of urban areas, high treatment-related costs, and long provider waitlists; highlighting the need to develop digitally delivered behavioural intervention, using agile and iterative study designs that support rapid development and timely dissemination. METHODS AND ANALYSIS: This study seeks to develop an effective and scalable intervention for youth with chronic pain and their caregivers. This paper presents a user-centred protocol for the development and refinement of a digital exposure treatment for youth and caregivers, as well as the study design to examine feasibility and preliminary efficacy of the treatment using single-case experimental design (SCED). Assessments include daily diaries, completed from baseline and daily throughout the intervention (~6 weeks), and at 3-month follow-up, as well as self-report measures completed at baseline, end of intervention and 3-month follow-up. Primary outcomes include treatment satisfaction, treatment expectancy, adherence to daily dairies and functional disability. Secondary outcomes are pain-related fear and avoidance of activities, pain catastrophising and pain acceptance. We will present descriptive and model-based inference analyses, based on SCED reporting guidelines. We will calculate effect sizes for each individual on each outcome. We will examine mean treatment expectancy, credibility and satisfaction scores, and patient drop-out percentage. ETHICS AND DISSEMINATION: This study is approved by the Institutional Review Board at Stanford University (protocol #53323). Findings will be actively disseminated through peer-reviewed journals, conference presentations and social media. TRIAL REGISTRATION NUMBER: NCT05079984.