Study protocol for a three-arm randomized controlled trial investigating the effectiveness, cost-utility, and physiological effects of a fully self-guided digital Acceptance and Commitment Therapy for Spanish patients with fibromyalgia.

Objective: Fibromyalgia (FM) is a prevalent pain syndrome with significant healthcare and societal costs. The aim of the SMART-FM-SP study is to determine the effectiveness, cost-utility, and physiological effects in patients with FM of a digital intervention (STANZA®) currently marketed in the United States, which delivers smartphone-based, fully self-guided Acceptance and Commitment Therapy (Digital ACT) for treating FM-related symptoms. Methods: A single-site, parallel-group, superiority, randomized controlled trial (RCT) will be conducted, including a total of 360 adults diagnosed with FM. Individuals will be randomly allocated (1:1:1) to treatment as usual (TAU), to TAU plus 12 weeks of treatment with Digital ACT, or to TAU plus 12 weeks of treatment with digital symptom tracking (i.e. FibroST). Participants will be assessed at baseline, post-treatment, and 6-month follow-up. An intention-to-treat analysis using linear mixed models will be computed to analyze the effects of Digital ACT on functional impairment (primary outcome), as measured by the Fibromyalgia Impact Questionnaire Revised at 6 months from the inception of the treatment. Secondary outcomes include impression of change, symptoms of distress, pain catastrophising, quality of life, cost-utility, and selected biomarkers (cortisol and cortisone, immune-inflammatory markers, and FKBP5 gene polymorphisms). The role of ACT-related processes of change will be tested with path analyses. Conclusions: This study is the first RCT that tests Digital ACT for Spanish patients with FM. Results will be important not only for patients and clinicians, but also for policy makers by examining the cost-utility of the app in a public healthcare context.

Definición de la fibromialgia / Definition of fibromyalgia

El artículo define brevemente la fibromialgia dentro de un contexto más amplio incluyendo las raíces históricas del concepto y su posible etiología, así como su interpretación dentro de los modelos biopsicosociales más actuales, con implicaciones terapéuticas de alto interés.(AU)

Women living with fibromyalgia during the COVID-19 pandemic: A qualitative study.

We explored the experiences of women with fibromyalgia during the COVID-19 pandemic from a qualitative approach by interviewing eighteen women. We identified seven main themes after performing a thematic analysis: pain description, pain triggers, impact, coping strategies, treatment for pain, pain onset and general situation. In general, pain worsened during the pandemic, and activity restrictions and changes in social interactions were particularly related with that. Pain negatively impacted different life domains: mental health, physical health, cognitive status, social activities and daily activities. Coping strategies varied slightly after the pandemic outbreak, and treatment was interrupted for some women. Results reflect that the pandemic was challenging for women living with fibromyalgia, and highlight the need to develop specific interventions for them in the context of potential future health emergencies.

Combining mindfulness and cognitive training in children with attention deficit hyperactivity disorder: study protocol of a pilot randomized controlled trial (the NeuroMind study).

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) has a global mean prevalence of 5%. Cognitive Training (CT) and Mindfulness-Based Interventions (MBIs) have shown promising results in managing ADHD symptoms, but they are not its Treatment-As-Usual (TAU). The NeuroMind Study aims to evaluate the preliminary effectiveness and feasibility of three interventions: Mindfulness for Health (M4H), CT using the NeuronUP® platform (CT), and a combination of both, Mindfulness Cognitive Training (MCT). There is empirical evidence supporting the effectiveness of the M4H and NeuronUP® platform; however, this study explores for the first time the effectiveness of MCT and CT, as well as the integration of M4H into TAU. The objectives of this 5-month Randomized Controlled Trial (RCT) are: (1) To analyze the preliminary effectiveness and feasibility of M4H, CT or a combination of both (MCT) added to TAU for children with ADHD; (2) To evaluate the role of psychological process variables (mindfulness and emotional regulation) as mediators of 5-month follow-up clinical outcomes; (3) To preliminarily explore whether specific sociodemographic and clinical characteristics can predict the short-and medium-term clinical response to the specific treatments. Methods and analysis: Participants will be 120 children (7 to 12 years) with ADHD recruited at Child and Adolescent Mental Health Service (CAMHS) Sant Joan de Déu Terres de Lleida (Spain) randomly allocated to one of the four study arms: TAU vs. TAU + CT vs. TAU + M4H vs. TAU + MCT. An assessment to collect ADHD symptoms, Executive Functions (EF), comorbid symptoms and global functioning will be conducted pre-intervention, post-intervention (2 months after baseline) and at the 5-month follow-up. Linear mixed models and mediational models will be computed. Discussion: If the preliminary effectiveness and feasibility of the MCT are demonstrated, this study could be a preliminary basis to do a full RCT with a larger sample to definitively validate the intervention. The MCT could be applied in clinical practice if it is definitively validated.Clinical trial registration:ClinicalTrials.gov, identifier, NCT05937347. https://clinicaltrials.gov/study/NCT05937347?locStr=Spain&country=Spain&cond=ADHD&intr=Mindfulness&rank=1.

Economic Evaluation of Videoconference Group Acceptance and Commitment Therapy and Behavioral Activation Therapy for Depression Versus Usual Care Among Adults With Chronic Low Back Pain Plus Comorbid Depressive Symptoms.

Chronic pain and depression are frequently comorbid conditions associated with significant health care and social costs. This study examined the cost-utility and cost-effectiveness of videoconference-based group forms of Acceptance and Commitment Therapy (ACT) and Behavioral Activation Therapy for Depression (BATD), as a complement to treatment-as-usual (TAU), for patients with chronic low back pain (CLBP) plus depressive symptoms, compared to TAU alone. A trial-based economic evaluation (n = 234) was conducted from a governmental and health care perspective with a time horizon of 12 months. Primary outcomes were the Brief Pain Inventory-Interference Scale (BPI-IS) and Quality Adjusted Life Year. Compared to TAU, ACT achieved a significant reduction in total costs (d = .47), and BATD achieved significant reductions in indirect (d = .61) and total costs (d = .63). Significant improvements in BPI-IS (d = .73 and d = .66, respectively) and Quality Adjusted Life Year scores (d = .46 and d = .28, respectively) were found in ACT and BATD compared to TAU. No significant differences in costs and outcomes were found between ACT and BATD. In the intention-to-treat analyses, from the governmental and health care perspective, no significant differences in cost reduction and incremental effects were identified in the comparison between ACT, BATD, and TAU. However, in the complete case analysis, significant incremental effects of ACT (∆BPI-IS = -1.57 and -1.39, respectively) and BATD (∆BPI-IS = -1.08 and -1.04, respectively) compared with TAU were observed. In the per-protocol analysis, only the significant incremental effects of ACT (∆BPI-IS = -1.68 and -1.43, respectively) compared to TAU were detected. In conclusion, ACT and BATD might be efficient options in the management of CLBP plus comorbid depression symptoms as compared to usual care. However, no clear difference was found in the comparison between the 2 active therapies regarding cost-effectiveness or cost-utility. PERSPECTIVE: The economic evaluation of psychological therapies for the management of complex conditions can be used in decision-making and resource allocation. This study provides evidence that ACT and BATD are more effective and involve a greater reduction in costs than usual care in the management of CLBP plus comorbid depressive symptoms. TRIAL NUMBER: NCT04140838.

Effectiveness of an online multicomponent program (FATIGUEWALK) for chronic fatigue syndrome: A randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the effectiveness of an online multicomponent intervention called FATIGUEWALK (FaW) compared to treatment as usual (TAU) in patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). METHOD: FaW included pain neuroscience education, therapeutic exercise, cognitive restructuring, and mindfulness training. A total of 428 patients with CFS/ME were randomized into two study arms: online FaW plus TAU versus TAU alone. A single-blinded randomized controlled trial was conducted. Validated patient-reported outcome measures of fatigue, pain, anxiety, depression, and physical function were collected at baseline and posttreatment, following the FaW intervention, which lasted 12 weeks. RESULTS: Statistically significant improvements (with small-to-moderate effect sizes) were observed in online FaW versus TAU alone with respect to multidimensional aspects of fatigue (Cohen's d ranging from 0.25 to 0.73) and most secondary outcomes (pain and fatigue intensity, depressive and anxious symptomatology, functional impairment, kinesiophobia, physical functioning). The absolute risk reduction in FaW versus TAU was 19%, 95% confidence interval (CI) [12.19, 25.80] with number needed to treat = 6, 95% CI [3.9, 8.2]. Overall, similar clinical improvements were observed in sensitivity analyses including a subgroup of patients without comorbidity with fibromyalgia (n = 70). CONCLUSIONS: This is the first study to assess the short-term effectiveness of an online multicomponent intervention added to TAU, compared to TAU alone, for the management of CFS/ME. Further trials, including active control groups with an equivalent treatment dose, and assessing the long-term effectiveness of the online FaW, are warranted. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Predictive factors of the psychological impact of the COVID-19 pandemic on university students: a study in six Ibero-American countries / Factores predictivos del impacto psicológico de la pandemia de COVID-19 en estudiantes universitarios: un estudio en seis países iberoamericanos

Background/Objective: During Covid-19, high prevalences of anxiety and depression were reported among university students, suggesting that they may be at higher risk than the general population of developing psychological disorders in lockdown situations. This study aimed to analyze how sociocultural factors and individual differences contributed to explaining the psychological impact of the pandemic among Ibero-American university students from Argentina, Colombia, Ecuador, Spain, Mexico, and Uruguay. Method: The study was carried out on 7601 university students (72% women). Data were collected through an online questionnaire that measured anxiety (GAD-2), depression (PHQ-2), somatic symptoms (SSQ-5), post-traumatic growth (PTGI), loneliness (UCLS), personality (NEO-FFI), Resilience (CD-RISC-2), Perceived Competences (PCS) and sociodemographic data. Descriptive statistics and multiple linear regression model were performed. Results: Analysis indicated a high prevalence (46.15%) of distress among university students, regardless of country and significantly higher than in the general population (28.27%). Greater feelings of loneliness and greater neuroticism were significantly associated with anxiety, depression, and somatization. Likewise, male gender and higher levels of resilience were found to be protective factors, while post-traumatic growth was also higher in men and was associated with higher levels of resilience, perceived competence, and responsibility. Conclusions: The results suggest the need to consider individual risk factors such as being a woman, presenting higher levels of neuroticism and loneliness in understanding the psychological impact of the pandemic on university students. It is concluded that universities should offer specific interventions to address mental health problems and manage the added complications of crisis events on the health of students.(AU)

Antecedentes/Objetivo: Durante el Covid-19, se informaron altas prevalencias de ansiedad y depresión entre estudiantes universitarios, lo que sugiere que pueden tener un mayor riesgo que la población general de desarrollar trastornos psicológicos en situaciones de encierro. Este estudio tuvo como objetivo analizar cómo los factores socioculturales y las diferencias individuales contribuyeron a explicar el impacto psicológico de la pandemia entre estudiantes universitarios iberoamericanos de Argentina, Colombia, Ecuador, España, México y Uruguay. Método: El estudio se realizó en 7601 estudiantes universitarios (72% mujeres). Los datos fueron recolectados a través de un cuestionario en línea que midió ansiedad (GAD-2), depresión (PHQ-2), síntomas somáticos (SSQ-5), crecimiento postraumático (PTGI), soledad (UCLS), personalidad (NEO-FFI), Resiliencia (CD-RISC-2), Competencia Percibida (PCS) y datos sociodemográficos. Se realizó estadística descriptiva y modelo de regresión lineal múltiple. Resultados: Los análisis indicaron una alta prevalencia (46,15%) de angustia entre los estudiantes universitarios, independientemente del país y significativamente mayor que en la población general (28,27%). Mayores sentimientos de soledad y mayor neuroticismo se asociaron significativamente con ansiedad, depresión y somatización. Asimismo, el género masculino y mayores niveles de resiliencia resultaron ser factores protectores, mientras que el crecimiento postraumático también fue mayor en los hombres y se asoció con mayores niveles de resiliencia, competencia percibida y responsabilidad. Conclusiones: Los resultados sugieren la necesidad de considerar factores de riesgo individuales como ser mujer, presentar mayores niveles de neuroticismo y soledad en la comprensión del impacto psicológico de la pandemia en estudiantes universitarios. Se concluye que las universidades deben ofrecer intervenciones específicas para abordar los problemas de salud mental y manejar las complicaciones añadidas de los eventos de crisis sobre la salud de los estudiantes.(AU)

Experiences of patients with chronic low back pain plus comorbid depressive symptoms in a videoconference group acceptance and commitment therapy or behavioral activation treatment for depression: a qualitative study.

PURPOSE: To explore the experiences of patients with chronic low back pain (CLBP) plus comorbid depressive symptoms who received a remote synchronous videoconference group form of Acceptance and Commitment Therapy (ACT) or Behavioral Activation Treatment for Depression (BATD). METHODS: A qualitative study (IMPACT-Q) was nested within a randomized controlled trial (RCT) designed to assess the efficacy and the cost-utility/cost-effectiveness of two therapies in the management of CLBP and depression. Fifty-five patients with CLBP plus depression were selected from the RCT. Twelve focus group sessions, each approximately 60-90 min long, were audio-recorded, transcribed verbatim, and analyzed by six coders through a thematic analysis (deductive and inductive) based on a descriptive phenomenological approach. RESULTS: Patients perceived behavioral, affective, and cognitive improvements after completing group sessions. Overall, psychotherapy was perceived as a safe and non-judgmental place to express emotions and feel understood. The main barriers reported were lack of human contact and loss of social interaction. In contrast, ease of access, flexibility in the ability to connect from anywhere, avoidance of the need to travel, and savings in time and money were key facilitators to increase attendance and adherence to therapy. CONCLUSION: This study provided support for the acceptability of videoconference-delivered ACT or BATD in patients with CLBP plus comorbid depressive symptoms.

Overall, patients reported behavioral, affective, and cognitive improvements after Acceptance and Commitment Therapy and Behavioral Activation Treatment for Depression group sessions.Acceptance and Commitment Therapy and Behavioral Activation Treatment for Depression delivered via videoconference platform were perceived as a facilitator for therapy attendance rather than a barrier.The findings indicate that group therapy on videoconferencing is perceived favorably as an alternative for managing patients with chronic pain and comorbid depression.Technical and social aspects of implementing videoconferencing therapies should be improved, as well as guidelines for adequate support for patients and therapists should also be provided.

Exploring the Relationship Between Self-Compassion and Compassion for Others: The Role of Psychological Distress and Wellbeing.

We addressed construct validity and explored the relationship between self-compassion and compassion for others using the two main current operationalizations of compassion (Neff's and the Sussex-Oxford Compassion Scales, SOCSs). Relationships with psychological distress and wellbeing, and potential differences in the association between self-compassion and compassion for others by level of psychological distress and wellbeing were also explored. Participants (n = 811) completed the Spanish adaptations of the Self-Compassion Scale (SCS), the Compassion Scale (CS), the SOCSs (for the self/others), the Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS), and the Depression Anxiety Stress Scales-21 (DASS-21). We fitted bifactor models to estimate the general factor of each construct for the different operationalizations, and calculated correlations between them. Relationships between self-compassion and compassion for others from the same operationalization were intermediate, while those between the same constructs from different operationalizations were large. Both constructs showed positive associations with wellbeing, while only self-compassion was associated with decreased psychological distress. Participants with good mental health showed higher associations between self-compassion and compassion for others than those with poorer mental health. Self-compassion and compassion for others appear to be dimensional constructs that can converge or diverge. When they converge, it is associated with better mental health.

The Role of Time Perspective and Mindfulness on Life Satisfaction in the United States of America, Spain, Poland and Japan: A Cross-Cultural Study.

We assessed the cross-cultural role of Time Perspective (TP) tendencies [Past Positive (PP), Past Negative (PN), Present Hedonistic (PH), Present Fatalistic (PF), and Future (F)], the Deviation from a Balanced Time Perspective (DBTP) profile, the Deviation from a Negative Time Perspective (DNTP) profile, and mindfulness on life satisfaction (LS). The sample consisted of psychology undergraduate students (N= 867, MAGE= 20.19, SD= 3.417) in four countries: USA, Spain, Poland and Japan. We used a 17-item short version of the Zimbardo Time Perspective Inventory (ZTPI), the Mindful Attention Awareness Scale (MAAS), and the Satisfaction with Life Scale (SWLS) in all countries. For ensuring measurement invariance, we conducted pairwise CFAs for the ZTPI-17, MAAS and SWLS. Regression analyses showed that PN predicted decreased LS in Poland and Japan. PP predicted increased LS in Spain. F predicted increased LS in Poland. DNTP predicted decreased LS in Poland. Mindfulness predicted decreased LS in Japan and increased LS in USA, Spain and Poland. Moreover, mediation analyses revealed that the DBTP partially mediated the relationship between mindfulness and LS in Spain and USA. The DNTP partially mediated the relationship between mindfulness and LS in Spain, Poland and Japan (opposite direction). The findings suggest that the association of TP, mindfulness and LS differs across the investigated countries as a function of culture.

The Toronto Mindfulness Scale and the State Mindfulness Scale: psychometric properties of the Spanish versions.

Objectives: The Toronto Mindfulness Scale (TMS) and the State Mindfulness Scale (SMS) are two relevant self-report measures of state mindfulness. The purpose of this study was to examine the internal structure and to offer evidence of the reliability and validity of the Spanish versions of the TMS and SMS. Methods: Data from six distinct non-clinical samples in Spain were obtained. They responded to the TMS (n = 119), SMS (n = 223), and measures of trait mindfulness, decentering, non-attachment, depression, anxiety, stress, positive and negative affect, self-criticism, and self-reassurance. The internal structure of the TMS and SMS was analyzed through confirmatory factor analysis. Reliability, construct validity, and sensitivity to change analyses were performed. Results: The correlated two-factor structure (curiosity and decentering) was the best-fitting model for the TMS (CFI = 0.932; TLI = 0.913; RMSEA = 0.100 [0.077-0.123]; WRMR = 0.908). The bifactor structure (general factor, mindfulness of body, and mindfulness of mind) was the best-fitting model for the SMS (CFI = 0.961; TLI = 0.950; RMSEA = 0.096 [0.086-0.106]; WRMR = 0.993). Adequate reliability was found for both measures. The reliability of the SMS specific factors was very poor when controlling for the general factor. The patterns of correlations were mainly as expected and according to previous literature. The TMS and SMS have been able to detect state mindfulness changes after different meditation practices. Conclusion: Validity evidence is provided to support the use of the TMS and SMS in Spanish populations, though the reliability of the SMS specific factors merit revision.

Efficacy of Videoconference Group Acceptance and Commitment Therapy (ACT) and Behavioral Activation Therapy for Depression (BATD) for Chronic Low Back Pain (CLBP) Plus Comorbid Depressive Symptoms: A Randomized Controlled Trial (IMPACT Study).

This study examined the efficacy of adding a remote, synchronous, group, videoconference-based form of acceptance and commitment therapy (ACT) or behavioral activation therapy for depression (BATD) to treatment-as-usual (TAU) in 234 patients with chronic low back pain (CLBP) plus comorbid depressive symptoms. Participants were randomly assigned to ACT, BATD, or TAU. Compared to TAU, ACT produced a significant reduction in pain interference at posttreatment (d = .64) and at follow-up (d = .73). BATD was only superior to TAU at follow-up (d = .66). A significant reduction in pain catastrophizing was reported by patients assigned to ACT and BATD at posttreatment (d = .45 and d = .59, respectively) and at follow-up (d = .59, in both) compared to TAU. Stress was significantly reduced at posttreatment by ACT in comparison to TAU (d = .69). No significant between-group differences were found in depressive or anxiety symptoms. Clinically relevant number needed to treat (NNT) values for reduction in pain interference were obtained at posttreatment (ACT vs TAU = 4) and at follow-up (ACT vs TAU = 3; BATD vs TAU = 5). In both active therapies, improvements in pain interference at follow-up were significantly related to improvements at posttreatment in psychological flexibility. These findings suggest that new forms of cognitive-behavioral therapy are clinically useful in improving pain interference and pain catastrophizing. Further research on evidence-based change processes is required to understand the therapeutic needs of patients with chronic pain and comorbid conditions. TRIAL NUMBER: NCT04140838. PERSPECTIVE: Group videoconference-based ACT and BATD showed greater efficacy than TAU for reducing pain interference and pain catastrophizing in patients with CLBP plus clinically relevant depression. Psychological flexibility appeared to be the main contributor to treatment effects for both ACT and BATD.

Predictive factors of hesitancy to vaccination against SARS-CoV-2 virus in young adults in Spain: Results from the PSY-COVID study.

Widespread population vaccination against the SARS-CoV-2 virus is a matter of great interest to public health as it is the main pharmacological measure to contain the COVID-19 pandemic. Hesitancy/reluctance to vaccination has become a main barrier to containing the pandemic. Young adults are the age group with the greatest resistance to vaccination, even in countries with the highest vaccination rates during this pandemic. The objective of this study was to identify the main predictive factors of vaccination intention and profile people with hesitancy/reluctance to vaccinate against SARS-CoV-2 virus in young adults living in Spain during the pandemic. A cross-sectional study was conducted based on the administration of an online survey (PSY-COVID-2) that evaluated the intention of vaccination together with a wide range of sociodemographic, social, cognitive, behavioral and affective variables in a sample of 2210 young adults. 14% of the sample showed hesitancy/reluctance to vaccination at the beginning of their vaccination campaign. A total of 35 factors were associated (small to medium effect sizes) with the intention to get vaccinated. A reduced set of 4 attitudinal and social variables explained 41% of the variability in vaccination intention: attitude to the vaccination, trust in health staff/scientists, conspiracy beliefs about SARS-CoV-2 and time spent being informed about COVID-19. These variables showed good sensitivity/specificity for classifying people as reluctant/not reluctant to vaccination, properly classifying 86% of people. Psychosocial processes related to attitudes, trust and information are the main predictors of vaccination intention in a highly reluctant group such as the young adult population.

How mindfulness, self-compassion, and experiential avoidance are related to perceived stress in a sample of university students.

University students constitute a population that is highly vulnerable to developing mental health problems, such as distress. The role of different variables associated with the development of states of stress has been studied in order to identify potential risk and protective factors. This study explored whether mindfulness, self-compassion, and experiential avoidance, while controlling for specific sociodemographic and academic variables, were potential significant protective or risk factors explaining perceived stress in a sample of 589 Spanish university students (81.2% female, age range 18-48 years). A hierarchical multiple regression analysis was performed using an exploratory cross-sectional design. Higher experiential avoidance, lower self-compassion, lower mindfulness, not perceiving family support, higher total study hours per week, having a partner (vs. being single), being female (vs. being male), and being older were significantly associated with higher levels of perceived stress. In conclusion, perceived stress in our sample was positively associated with experiential avoidance, which could be regarded as a potential psychological risk variable. In contrast, perceived stress was negatively correlated with self-compassion and mindfulness, which, in turn, could be seen as protective factors. Accordingly, it is concluded that programmes aimed at reducing stress and at improving well-being among university students should include experiential avoidance, self-compassion, and mindfulness as therapeutic targets.

A systematic review of cognitive behavioral therapy-based interventions for comorbid chronic pain and clinically relevant psychological distress.

Objective: Chronic pain frequently co-occurs with clinically relevant psychological distress. A systematic review was conducted to identify the efficacy of cognitive behavioral therapy-based interventions for patients with these comorbid conditions. Methods: The systematic search was carried out in Medline, PsycINFO, Web of Science, and Scopus up to March 18th, 2023. Four reviewers independently conducted screenings, extraction, and quality assessment. Results: Twelve randomized controlled trials and one non-randomized controlled trial involving 1,661 participants that examined the efficacy of Cognitive Behavioral Therapy (nine studies), Mindfulness-based Interventions (three studies), Acceptance and Commitment Therapy (one study), and Behavioral Activation Therapy for Depression (one study) were included. Compared to treatment as usual, six out of eight studies of traditional Cognitive Behavioral Therapy reported significant differences in the reduction of depressive symptoms at post-treatment (d from 1.31 to 0.18) and four out of six at follow-up (d from 0.75 to 0.26); similarly, five out of six reported significant differences in the reduction of anxiety symptoms at post-treatment (d from 1.08 to 0.19) and three out of four at follow-up (d from 1.07 to 0.27). Overall, no significant differences between traditional Cognitive Behavioral Therapy and treatment as usual were reported at post-treatment and follow-up in the studies exploring pain intensity and pain catastrophizing. Conclusion: The available evidence suggests that traditional Cognitive Behavioral Therapy may produce significant benefits for the improvement of depression, anxiety, and quality of life, but not for pain intensity and pain catastrophizing. More evidence is needed to determine the effects of MBI, ACT, and BATD. Systematic review registration: PROSPERO, CRD42021219921.

Effectiveness, cost-utility and physiological underpinnings of the FIBROWALK multicomponent therapy in online and outdoor format in individuals with fibromyalgia: Study protocol of a randomized, controlled trial (On&Out study).

Introduction: The On&Out study is aimed at assessing the effectiveness, cost-utility and physiological underpinnings of the FIBROWALK multicomponent intervention conducted in two different settings: online (FIBRO-On) or outdoors (FIBRO-Out). Both interventions have proved to be efficacious in the short-term but there is no study assessing their comparative effectiveness nor their long-term effects. For the first time, this study will also evaluate the cost-utility (6-month time-horizon) and the effects on immune-inflammatory biomarkers and Brain-Derived Neurotrophic Factor (BDNF) levels of both interventions. The objectives of this 6-month, randomized, controlled trial (RCT) are 1) to examine the effectiveness and cost-utility of adding FIBRO-On or FIBRO-Out to Treatment-As-Usual (TAU) for individuals with fibromyalgia (FM); 2) to identify pre-post differences in blood biomarker levels in the three study arms and 3) to analyze the role of process variables as mediators of 6-month follow-up clinical outcomes. Methods and analysis: Participants will be 225 individuals with FM recruited at Vall d'Hebron University Hospital (Barcelona, Spain), randomly allocated to one of the three study arms: TAU vs. TAU + FIBRO-On vs. TAU + FIBRO-Out. A comprehensive assessment to collect functional impairment, pain, fatigue, depressive and anxiety symptoms, perceived stress, central sensitization, physical function, sleep quality, perceived cognitive dysfunction, kinesiophobia, pain catastrophizing, psychological inflexibility in pain and pain knowledge will be conducted pre-intervention, at 6 weeks, post-intervention (12 weeks), and at 6-month follow-up. Changes in immune-inflammatory biomarkers [i.e., IL-6, CXCL8, IL-17A, IL-4, IL-10, and high-sensitivity C-reactive protein (hs-CRP)] and Brain-Derived Neurotrophic Factor will be evaluated in 40 participants in each treatment arm (total n = 120) at pre- and post-treatment. Quality of life and direct and indirect costs will be evaluated at baseline and at 6-month follow-up. Linear mixed-effects regression models using restricted maximum likelihood, mediational models and a full economic evaluation applying bootstrapping techniques, acceptability curves and sensitivity analyses will be computed. Ethics and dissemination: This study has been approved by the Ethics Committee of the Vall d'Hebron Institute of Research. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media and various community engagement activities. Trial registration number NCT05377567 (clinicaltrials.gov).

Effectiveness of two video-based multicomponent treatments for fibromyalgia: The added value of cognitive restructuring and mindfulness in a three-arm randomised controlled trial.

BACKGROUND/OBJECTIVES: The aim of this study was to examine the effectiveness of two video-based multicomponent programs (FIBROWALK) and the Multicomponent Physiotherapy Program (MPP) for patients with fibromyalgia (FM) compared to treatment-as-usual (TAU) only. We posit that FIBROWALK, due to inclusion of specific psychological ingredients (cognitive restructuring and mindfulness), can produce additional clinical benefits when compared to TAU or MPP alone. METHODS: A total of 330 patients with FM were recruited and randomly allocated (1:1:1) to TAU only, TAU + FIBROWALK, or TAU + MPP. FIBROWALK and MPP consisted of weekly videos on pain neuroscience education, therapeutic exercise and self-management patient education, but only the FIBROWALK intervention provided cognitive restructuring and mindfulness. Both programs were structurally equivalent. Between-group differences in functional impairment, pain, kinesiophobia, anxious-depressive symptoms and physical functioning were evaluated at post-treatment following Intention-To-Treat and complete-case approaches. RESULTS: Compared to TAU only, individuals in the FIBROWALK arm showed larger improvements in all clinical outcomes; similarly, participants in the MPP program also showed greater improvements in functional impairment, perceived pain, kinesiophobia, depressive symptoms compared to TAU only. The FIBROWALK intervention showed superior effects in improving pain, anxiety and depressive symptoms and physical functioning compared to MPP. CONCLUSIONS: This RCT supports the short-term effectiveness of the video-based multicomponent programs FIBROWALK and MPP for FM and provides evidence that cognitive-behavioural and mindfulness-based techniques can be clinically useful in the context of physiotherapeutic multicomponent treatment programs. TRIAL REGISTRATION NUMBER: NCT04571528.

Immune-inflammatory and hypothalamic-pituitary-adrenal axis biomarkers are altered in patients with non-specific low back pain: A systematic review.

This systematic review aimed to investigate immune-inflammatory and hypothalamic-pituitary-adrenal (HPA) axis biomarkers in individuals with non-specific low back pain (NSLBP) compared to healthy control. The search was performed in five databases until 4 November 2021. Two reviewers independently conducted screenings, data extraction, risk of bias, and methodological quality assessment of 14 unique studies. All studies reported the source of the fluid analyzed: nine studies used serum, two used plasma, one used serum and plasma, and two studies used salivary cortisol. We found preliminary and limited evidence (only one study for each biomarker) of increased levels in growth differentiation factor 15 (GDF-15), interleukin-23 (IL-23), transforming growth factor-beta (TGF-ß), and soluble tumor necrosis factor receptor 1 (sTNF-R1) in NSLBP. Inconsistent and limited evidence was identified for interleukin-10 (IL-10). Although C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels appear to increase in NSLBP, only one study per each biomarker reported statistically significant differences. Interleukin-1 beta (IL-1ß), interleukin-17 (IL-17), interferon gamma (IFN-γ), and high-sensitivity CRP (hsCRP) showed no significant differences. Regarding cortisol, one study showed a significant increase and another a significant decrease. More robust evidence between GDF-15, IL-23, TGF-ß, and sTNF-R1 with NSLBP is needed. Moreover, contrary to the findings reported in previous studies, when comparing results exclusively with healthy control, insufficient robust evidence for IL-6, TNF-α, and CRP was found in NSLBP. In addition, cortisol response (HPA-related biomarker) showed a dysregulated functioning in NSLBP, with incongruent evidence regarding its directionality. Therefore, our effort is to find adjusted evidence to conclude which immune-inflammatory and HPA axis biomarkers are altered in NSLBP and how much their levels are affected. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020176153, identifier CRD42020176153.

Differential Brain Perfusion Changes Following Two Mind-Body Interventions for Fibromyalgia Patients: an Arterial Spin Labelling fMRI Study.

OBJECTIVES: Further mechanistic insight on mind-body techniques for fibromyalgia (FMS) is needed. Arterial spin labelling (ASL) imaging can capture changes in regional cerebral blood flow (rCBF) that relate to spontaneous pain. METHODS: We recruited FMS patients undergoing either mindfulness-based stress reduction training (MBSR, n = 14) or a psychoeducational programme (FibroQoL, n = 18), and a control FMS group with no add-on treatment (n = 14). We acquired whole-brain rCBF maps and self-report measures at baseline and following treatment and explored interaction effects in brain perfusion between the treatment group and session with a focus on the amygdala, the insula and the anterior cingulate cortex (ACC). RESULTS: We identified a significant interaction effect in the amygdala, which corresponded with rCBF decreases following FibroQoL specifically. At baseline, rCBF in the amygdala for the FibroQoL group correlated with pain catastrophizing and anxiety scores, but not after treatment, suggesting a decoupling between activity in the amygdala and negative emotional symptoms of FMS as a consequence of treatment. Baseline rCBF correlated positively with pain symptoms in the ACC and the anterior insula across all patients; moreover, the correlation between rCBF changes post intervention in the insula and pain improvement was negative for both treatments and significantly different from the control group. We suggest that there is disruption of the typical relationship between clinical pain and activity as a product of these two nonpharmacological therapies. CONCLUSIONS: We have demonstrated that different mind-to-body treatments correspond to differential changes in clinical symptoms and brain activity patterns, which encourages future research investigating predictors of treatment response. TRIAL REGISTRATION:  NCT02561416. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12671-021-01806-2.

Study protocol for a randomised, double-blinded, placebo-controlled phase III trial examining the add-on efficacy, cost-utility and neurobiological effects of low-dose naltrexone (LDN) in patients with fibromyalgia (INNOVA study).

INTRODUCTION: There is evidence that low-dose naltrexone (LDN; <5.0 mg/day) reduces pain and improves the quality of life of people with fibromyalgia syndrome (FMS). However, no randomised controlled trials with long-term follow-ups have been carried out. The INNOVA study will evaluate the add-on efficacy, safety, cost-utility and neurobiological effects of LDN for reducing pain in patients with FMS, with a 1-year follow-up. METHODS AND ANALYSIS: A single-site, prospective, randomised, double-blinded, placebo-controlled, parallel design phase III trial will be performed. Eligibility criteria include being adult, having a diagnosis of FMS and experiencing pain of 4 or higher on a 10-point numerical rating scale. Participants will be randomised to a LDN intervention group (4.5 mg/day) or to a placebo control group. Clinical assessments will be performed at baseline (T0), 3 months (T1), 6 months (T2) and 12 months (T3). The primary endpoint will be pain intensity. A sample size of 60 patients per study arm (120 in total), as calculated prior to recruitment for sufficient power, will be monitored between January 2022 and August 2024. Assessment will also include daily ecological momentary evaluations of FMS-related symptoms (eg, pain intensity, fatigue and sleep disturbance), and side effects via ecological momentary assessment through the Pain Monitor app during the first 3 months. Costs and quality-adjusted life years will be also calculated. Half of the participants in each arm will be scanned with MRI at T0 and T1 for changes in brain metabolites related to neuroinflammation and central sensitisation. Inflammatory biomarkers in serum will also be measured. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the Fundació Sant Joan de Déu. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media and community engagement activities. TRIAL REGISTRATION NUMBER: NCT04739995.