Feasibility and Acceptability of Biofeedback-Based Virtual Reality System Use in Children and Adolescents Undergoing Surgery: Phase 1 of a Pilot Observational Study.

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.

Effectiveness of population-based recovery actions for threatened southern mountain caribou.

Habitat loss is affecting many species, including the southern mountain caribou (Rangifer tarandus caribou) population in western North America. Over the last half century, this threatened caribou population's range and abundance have dramatically contracted. An integrated population model was used to analyze 51 years (1973-2023) of demographic data from 40 southern mountain caribou subpopulations to assess the effectiveness of population-based recovery actions at increasing population growth. Reducing potential limiting factors on threatened caribou populations offered a rare opportunity to identify the causes of decline and assess methods of recovery. Southern mountain caribou abundance declined by 51% between 1991 and 2023, and 37% of subpopulations were functionally extirpated. Wolf reduction was the only recovery action that consistently increased population growth when applied in isolation, and combinations of wolf reductions with maternal penning or supplemental feeding provided rapid growth but were applied to only four subpopulations. As of 2023, recovery actions have increased the abundance of southern mountain caribou by 52%, compared to a simulation with no interventions. When predation pressure was reduced, rapid population growth was observed, even under contemporary climate change and high levels of habitat loss. Unless predation is reduced, caribou subpopulations will continue to be extirpated well before habitat conservation and restoration can become effective.

Season, prey availability, sex, and age explain prey size selection in a large solitary carnivore.

Prey selection is a fundamental aspect of ecology that drives evolution and community structure, yet the impact of intraspecific variation on the selection for prey size remains largely unaccounted for in ecological theory. Here, we explored puma (Puma concolor) prey selection across six study sites in North and South America. Our results highlighted the strong influence of season and prey availability on puma prey selection, and the smaller influence of puma age. Pumas in all sites selected smaller prey in warmer seasons following the ungulate birth pulse. Our top models included interaction terms between sex and age, suggesting that males more than females select larger prey as they age, which may reflect experiential learning. When accounting for variable sampling across pumas in our six sites, male and female pumas killed prey of equivalent size, even though males are larger than females, challenging assumptions about this species. Nevertheless, pumas in different study sites selected prey of different sizes, emphasizing that the optimal prey size for pumas is likely context-dependent and affected by prey availability. The mean prey weight across all sites averaged 1.18 times mean puma weight, which was less than predicted as the optimal prey size by energetics and ecological theory (optimal prey = 1.45 puma weight). Our results help refine our understanding of optimal prey for pumas and other solitary carnivores, as well as corroborate recent research emphasizing that carnivore prey selection is impacted not just by energetics but by the effects of diverse ecology.

Annotated genome and transcriptome of the endangered Caribbean mountainous star coral (Orbicella faveolata) using PacBio long-read sequencing.

Long-read sequencing is revolutionizing de-novo genome assemblies, with continued advancements making it more readily available for previously understudied, non-model organisms. Stony corals are one such example, with long-read de-novo genome assemblies now starting to be publicly available, opening the door for a wide array of 'omics-based research. Here we present a new de-novo genome assembly for the endangered Caribbean star coral, Orbicella faveolata, using PacBio circular consensus reads. Our genome assembly improved the contiguity (51 versus 1,933 contigs) and complete and single copy BUSCO orthologs (93.6% versus 85.3%, database metazoa_odb10), compared to the currently available reference genome generated using short-read methodologies. Our new de-novo assembled genome also showed comparable quality metrics to other coral long-read genomes. Telomeric repeat analysis identified putative chromosomes in our scaffolded assembly, with these repeats at either one, or both ends, of scaffolded contigs. We identified 32,172 protein coding genes in our assembly through use of long-read RNA sequencing (ISO-seq) of additional O. faveolata fragments exposed to a range of abiotic and biotic treatments, and publicly available short-read RNA-seq data. With anthropogenic influences heavily affecting O. faveolata, as well as its increasing incorporation into reef restoration activities, this updated genome resource can be used for population genomics and other 'omics analyses to aid in the conservation of this species.

Genomic epidemiology of third-generation cephalosporin-resistant Escherichia coli from Argentinian pig and dairy farms reveals animal-specific patterns of co-resistance and resistance mechanisms.

Control measures are being introduced globally to reduce the prevalence of antibiotic resistance (ABR) in bacteria on farms. However, little is known about the current prevalence and molecular ecology of ABR in bacterial species with the potential to be key opportunistic human pathogens, such as Escherichia coli, on South American farms. Working with 30 dairy cattle farms and 40 pig farms across two provinces in central-eastern Argentina, we report a comprehensive genomic analysis of third-generation cephalosporin-resistant (3GC-R) E. coli, which were recovered from 34.8% (cattle) and 47.8% (pigs) of samples from fecally contaminated sites. Phylogenetic analysis revealed substantial diversity suggestive of long-term horizontal and vertical transmission of 3GC-R mechanisms. CTX-M-15 and CTX-M-2 were more often produced by isolates from dairy farms, while CTX-M-8 and CMY-2 and co-carriage of amoxicillin/clavulanate resistance and florfenicol resistance were more common in isolates from pig farms. This suggests different selective pressures for antibiotic use in these two animal types. We identified the ß-lactamase gene blaROB, which has previously only been reported in the family Pasteurellaceae, in 3GC-R E. coli. blaROB was found alongside a novel florfenicol resistance gene, ydhC, also mobilized from a pig pathogen as part of a new composite transposon. As the first comprehensive genomic survey of 3GC-R E. coli in Argentina, these data set a baseline from which to measure the effects of interventions aimed at reducing on-farm ABR and provide an opportunity to investigate the zoonotic transmission of resistant bacteria in this region. IMPORTANCE: Little is known about the ecology of critically important antibiotic resistance among bacteria with the potential to be opportunistic human pathogens (e.g., Escherichia coli) on South American farms. By studying 70 pig and dairy cattle farms in central-eastern Argentina, we identified that third-generation cephalosporin resistance (3GC-R) in E. coli was mediated by mechanisms seen more often in certain species and that 3GC-R pig E. coli were more likely to be co-resistant to florfenicol and amoxicillin/clavulanate. This suggests that on-farm antibiotic usage is key to selecting the types of E. coli present on these farms. 3GC-R E. coli and 3GC-R plasmids were diverse, suggestive of long-term circulation in this region. We identified the de novo mobilization of the resistance gene blaROB from pig pathogens into E. coli on a novel mobile genetic element, which shows the importance of surveying poorly studied regions for antibiotic resistance that might impact human health.

Associations between patient-reported functional disability and measures of physical ability in juvenile fibromyalgia.

ABSTRACT: Juvenile fibromyalgia (JFM) is a chronic condition characterized by symptoms of pain and fatigue and is associated with sedentary behavior and functional disability. Adults with fibromyalgia exhibit deficits in physical fitness as evidenced by lower aerobic capacity and physical endurance, but it is unknown whether these impairments are apparent in adolescents with JFM. Furthermore, the extent to which functional disability and pain interference relate to measures of physical fitness has not been investigated in a pediatric pain population. During a baseline assessment for a clinical trial, 321 adolescents with juvenile fibromyalgia (M age = 15.14, 85.2% female) completed measures of pain intensity, fatigue, JFM symptom severity, functional disability, and pain interference. They also completed 2 validated fitness tasks: (1) the Harvard step test, which assesses aerobic fitness, and (2) the 6-minute walk test, a simple submaximal test of endurance. We examined associations among self-report measures and fitness assessments using bivariate correlations. We then employed hierarchical regression analyses to determine the unique contributions of physical fitness assessments to self-reported functional disability and pain interference. Results indicated that youth with JFM exhibited deficits in aerobic capacity and physical endurance. However, physical fitness explained negligible variance in functional disability and pain interference beyond that accounted for by pain, fatigue, and JFM symptom severity. Scores on available functional disability measures may reflect perceived difficulties in coping with symptoms during physical tasks rather than actual physical capability. Rigorous and sensitive assessments of physical fitness and endurance are needed to determine whether rehabilitation interventions for pediatric pain improve physical functioning.

A holistic biopsychosocial management approach for cis-gender males with chronic pelvic pain syndrome attending sexual health services: a retrospective case review.

OBJECTIVES: Chronic pelvic pain syndrome (CPPS) in men is a condition associated with significant morbidity which is typically managed in sexual health services. We introduced a modified biopsychosocial approach for managing CPPS in men, reducing use of antibiotics and evaluated its application in a retrospective case review. METHODS: Patients attended for a full consultation covering symptomology, onset and social history. Examination included urethral smear and assessment of pelvic floor tension and pain. A focus on pelvic floor relaxation was the mainstay of management with pelvic floor physiotherapy if required. Prescribing of antibiotics being discontinued if no evidence of urethritis at first consultation. The main outcome was change in the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score (which patients completed at each attendance); significant clinical improvement was defined as a NIH-CPSI score reduction of >25% and/or ≥6 points. RESULTS: Among 77 consecutive patients diagnosed with CPPS between April 2017 and December 2018, the mean NIH-CPSI score at the initial visit was 24.1 (11-42). Antibiotics were prescribed to 38/77 (49.4%) and alpha-blockers to 58/77 (75.3%). Overall, 50 (64.9%) patients with a mean initial NIH-CPSI score of 25.4 (11-42) re-attended a CPPS clinic. Among these, the average NIH-CPSI score at the final CPPS clinic appointment declined to 15.9 (0-39) (p<0.001); 34/50 (68%) men experienced significant clinical improvement. Men who attended only one CPPS clinic compared with those who reattended had a shorter duration of symptoms (18 (1-60) vs 36 (1-240) months; p=0.038), a lower initial NIH-CPSI score (21.7 (11-34) vs 25.4 (11-44); p=0.021), but had attended a similar number of clinics prior to referral (2.9 (0-6) vs 3.2 (0-8); p=0.62). CONCLUSIONS: The biopsychosocial approach significantly reduced the NIH-CPSI score in those who re-attended, with 68% of patients having a significant clinical improvement. The first follow-up consultation at 6 weeks is now undertaken by telephone for many patients, if clinically appropriate.

The effects of joint hypermobility on pain and functional biomechanics in adolescents with juvenile fibromyalgia: secondary baseline analysis from a pilot randomized controlled trial.

BACKGROUND: Joint hypermobility is a common clinical finding amongst hereditary connective tissue disorders that is observed in pediatric rheumatological settings, and often associated with chronic pain. Joint hypermobility may also contribute to deficits in physical functioning and physical activity, but previous findings have been inconsistent. It is possible that physical activity impairment in joint hypermobility may be due to chronic aberrant movement patterns subsequent to increased joint laxity. METHOD: As part of a larger randomized pilot trial of juvenile onset fibromyalgia (JFM), a secondary analysis was conducted to explore whether adolescents with JFM and joint hypermobility differed from non-joint hypermobility peers in terms of pain, daily functioning, and biomechanics (i.e., kinetics and kinematics) during a moderately vigorous functional task. RESULTS: From the larger sample of adolescents with JFM (N = 36), 13 adolescents (36.1%) met criteria for joint hypermobility and 23 did not have joint hypermobility. Those with joint hypermobility exhibited poorer overall functioning (Md = 20, Q1,Q3 [5.8, 7.6] vs. Md = 29, Q1,Q3 [5.1, 7.6]) but there were no differences in pain (Md = 6.9, Q1,Q3 [22, 33], vs. Md = 6.45, Q1,Q3 [15, 29.5]). Inspection of time-series plots suggests those with joint hypermobility exhibited decreased hip flexion and frontal plane hip moment (e.g., resistance to dynamic valgus) during the landing phase (early stance) and greater hip and knee transverse plane moments during the propulsion phase (late stance) of the drop vertical jump task (DVJ). No other differences in lower extremity biomechanics were observed between study groups. CONCLUSIONS: In this exploratory study, there were small but notable differences in biomechanics between patients with JFM who also had joint hypermobility versus those without joint hypermobility during a landing and jumping task (e.g., DVJ). These differences may indicate decreased joint stiffness during landing, associated with increased joint laxity and decreased joint stability, which may put them at greater risk for injury. Further study with a larger sample size is warranted to examine whether these biomechanical differences in patients with JFM and joint hypermobility affect their response to typical physical therapy or exercise recommendations.

The Association Between Family Resources and Language Among Young Children Who are Deaf and Hard of Hearing.

OBJECTIVE: Our study (1) examined demographic factors in families with children with bilateral hearing loss and how they relate to Family Resource Scale (FRS) questionnaire data and (2) examined correlations between FRS data and measures of language. METHODS: Children aged 6 months to 10 years with bilateral hearing loss were enrolled. Parents completed the FRS questionnaire to assess their access to socioeconomic resources at the first language measurement visit. Assessments measured receptive and expressive language, nonverbal intelligence quotient, and adaptive functioning. RESULTS: Among the 85 children included in the analysis, approximately 40% had hearing loss classified as mild to moderate and 25% had a cochlear implant. Participants' mean FRS score was 130 (SD 16.6) (with the highest possible score of 150 and indicating better access to resources). Significant positive correlations ( p -value ≤ 0.05) were found between maternal education, paternal education, and family income and several FRS subscales (Growth and Support, Necessities in Health, Childcare, Personal Resources). Significant positive correlations were found between the Necessities in Health subscale and all the language measurements. CONCLUSION: Children whose parents reported better access to socioeconomic resources related to health care had higher language performance scores. Although early access to intervention services has improved for deaf or hard-of-hearing children, there are other variables contributing to language development, including access to socioeconomic resources. This study highlights the need for further research addressing more specific and modifiable resources to improve language performance for deaf or hard-of-hearing children.

A narrative review of the literature on illness uncertainty in hypermobile ehlers-danlos syndrome: implications for research and clinical practice.

BACKGROUND: 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. CONCLUSION: 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.

Dataset used to refine a treatment protocol of a biofeedback-based virtual reality intervention for pain and anxiety in children and adolescents undergoing surgery.

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.

Feasibility and acceptability of perioperative application of biofeedback-based virtual reality versus active control for pain and anxiety in children and adolescents undergoing surgery: protocol for a pilot randomised controlled trial.

INTRODUCTION: Current clinical applications of virtual reality (VR) provide patients with transient pain relief during acutely painful events by redirecting attention. Biofeedback (BF) is a mind-body therapy that effectively produces sustained pain reduction, but there are obstacles to its routine use. Combined, BF-based VR (VR-BF) may increase accessibility while enhancing the benefits of BF. VR-BF has yet to be employed in perioperative care, and as such, no defined treatment protocol for VR-BF exists. The primary aim of this study is to assess the feasibility of the perioperative use of VR-BF in children and adolescents. The secondary aims are to assess the acceptability of VR-BF and to collect pilot efficacy data. METHODS AND ANALYSIS: This is a single-centre, randomised controlled pilot clinical trial. A total of 70 patients (12-18 years) scheduled for surgery anticipated to cause moderate to severe pain with ≥1 night of hospital admission will be randomised to one of two study arms (VR-BF or control). Participants randomised to VR-BF (n=35) will use the ForeVR VR platform to engage their breathing in gamified VR applications. Participants randomised to control (n=35) will interact with a pain reflection app, Manage My Pain. The primary outcome is feasibility of VR-BF use in adolescents undergoing surgery as assessed through recruitment, enrolment, retention and adherence to the protocol. Secondary outcomes are acceptability of VR-BF and pilot efficacy measures, including pain, anxiety and opioid consumption. ETHICS AND DISSEMINATION: The protocol was approved by the Nationwide Children's Hospital Institutional Review Board (IRB #STUDY00002080). Patient recruitment begins in March 2023. Written informed consent is obtained for all participants. All information acquired will be disseminated via scientific meetings and published in peer-reviewed journals. Data will be available per request and results will be posted on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04943874).

Clinical Characterization of Juvenile Fibromyalgia in a Multicenter Cohort of Adolescents Enrolled in a Randomized Clinical Trial.

OBJECTIVE: Juvenile fibromyalgia (JFM) is a complex chronic pain condition that remains poorly understood. The study aimed to expand the clinical characterization of JFM in a large representative sample of adolescents with JFM and identify psychological factors that predict pain interference. METHODS: Participants were 203 adolescents (ages 12-17 years) who completed baseline assessments for the multisite Fibromyalgia Integrative Training for Teens (FIT Teens) randomized control trial. Participants completed the Pain and Symptom Assessment Tool, which includes a Widespread Pain Index (WPI; 0-18 pain locations) and Symptom Severity checklist of associated somatic symptoms (SS; 0-12) based on the 2010 American College of Rheumatology criteria for fibromyalgia. Participants also completed self-report measures of pain intensity, functional impairment, and psychological functioning. RESULTS: Participants endorsed a median of 11 painful body sites (WPI score) and had a median SS score of 9. Fatigue and nonrestorative sleep were prominent features and rated as moderate to severe by 85% of participants. Additionally, neurologic, autonomic, gastroenterologic, and psychological symptoms were frequently endorsed. The WPI score was significantly correlated with pain intensity and catastrophizing, while SS scores were associated with pain intensity and all domains of physical and psychological functioning. Depressive symptoms, fatigue, and pain catastrophizing predicted severity of pain impairment. CONCLUSION: JFM is characterized by chronic widespread pain with fatigue, nonrestorative sleep, and other somatic symptoms. However, how diffusely pain is distributed appears less important to clinical outcomes and impairment than other somatic and psychological factors, highlighting the need for a broader approach to the assessment and treatment of JFM.

Telehealth for Pediatric Disorders of Gut-Brain Interaction During the COVID-19 Pandemic.

A retrospective chart review was completed to examine psychological treatment duration and response among pediatric patients with a disorder of gut-brain interaction including functional abdominal pain and irritable bowel syndrome. Cognitive behavioral therapy (CBT) was delivered via telehealth with a licensed psychologist or supervised psychology trainee embedded in a pediatric gastroenterology clinic. Participants were 22 youth (mean age = 14.36 years) who received CBT via telehealth between February and September of 2021, after completing an initial evaluation between February and July of 2021. Patients completed reliable and valid self-report measures of functional disability and pain during treatment. A unique CBT model was employed with an initial focus on psychoeducation and function regardless of level of severity of functional impairment. Consistent with study hypotheses, nonparametric statistical analyses demonstrated statistically significant reductions in functional disability and pain following implementation of the CBT model via telehealth. Contrary to predictions, there was no relation found between severity of functional impairment and duration of treatment.

FIT Teens RCT for juvenile fibromyalgia: Protocol adaptations in response to the COVID 19 pandemic.

Objective: 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. Design/methods: 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. Results: 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. Conclusions: 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.

Observable Symptoms of Anxiety in Individuals with Fragile X Syndrome: Parent and Caregiver Perspectives.

Caregiver reports, clinical observations, and diagnostic assessments indicate that most individuals with fragile X syndrome experience high levels of chronic anxiety. However, anxiety is a challenging endpoint for outcome measurement in FXS because most individuals cannot reliably report internal emotional or body states. A comprehensive survey of the presence, frequency, and duration of anxiety-related symptoms and questions to elicit open-ended responses was completed by caregivers of 456 individuals with FXS, ages 2-81 years (87 female, 369 male) and 24 female and 2 male FXS self-advocates ages 15-66 years. Caregivers reported classic behavioral indicators of anxiety, such as avoidance, irritability, motor agitation, and physiological symptoms, as well as behavioral features in FXS such as repetitive behavior, aggression, and self-injury. Self-advocate accounts largely paralleled caregiver data. Factor analyses yielded four factors: (1) increased irritability, aggression, and self-injury; (2) increased physical movement, nervous activity, and restlessness; (3) physical and physiological features of anxiety; and (4) internalizing and gastrointestinal symptoms. Caregivers are capable of observing and reporting behaviors that are valid indicators of anxious states that are usually reported in self-report standardized assessments. These results support the development of an anxiety measure for FXS that minimizes problems with rater inference.

Design and implementation of a novel patient-centered empowerment approach for pain optimisation in children undergoing major surgery.

BACKGROUND: Paediatric surgery is a stressful experience for patients and caregivers. While standardised protocols are the norm, patient-centred approaches are needed to empower patients/caregivers for an optimal perioperative pain experience. To address this gap, we employed a patient-centred approach using design thinking (DT) methodology to develop insights, map processes, identify opportunities and design solutions for individualised empowerment tools. METHODS: In consultation with DT experts, a multidisciplinary team of stakeholders (healthcare providers, patients who underwent pectus excavatum/scoliosis surgery and their caregivers), were invited to participate in surveys, interviews and focus groups. The project was conducted in two sequential stages each over 24 weeks-involving 7 families in stage 1 and 16 patients/17 caregivers in stage 2. Each stage consisted of three phases: design research (focus groups with key stakeholders to review and apply collective learnings, map processes, stressors, identify influencing factors and opportunities), concept ideation (benchmarking and co-creation of new solutions) and concept refinement. RESULTS: In stage 1, mapping of stress/anxiety peaks identified target intervention times. We identified positive and negative influencers as well as the need for consistent messaging from the healthcare team in our design research. Current educational tools were benchmarked, parent-child engagement dyads determined and healthcare-based technology-based solutions conceived. The 'hero's journey' concept which has been applied to other illness paradigms for motivation successfully the was adapted to describe surgery as a transformative experience. In stage 2, patient and caregiver expectations, distinct personas and responses to perioperative experience were categorised. Educational tools and an empowerment tool kit based on sensorial, thinking, relaxation and activity themes, tailored to parent/child categories were conceptualised. CONCLUSION: DT methodology provided novel family centred insights, enabling design of tailored empowerment toolkits to optimise perioperative experience. Adapting the hero's journey call to adventure may motivate and build resilience among children undergoing surgery.

Signature for Pain Recovery IN Teens (SPRINT): protocol for a multisite prospective signature study in chronic musculoskeletal pain.

INTRODUCTION: 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. METHODS AND ANALYSIS: 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. ETHICS AND DISSEMINATION: 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. TRIAL REGISTRATION NUMBER: NCT04285112.

Geographically driven differences in microbiomes of Acropora cervicornis originating from different regions of Florida's Coral Reef.

Effective coral restoration must include comprehensive investigations of the targeted coral community that consider all aspects of the coral holobiont-the coral host, symbiotic algae, and microbiome. For example, the richness and composition of microorganisms associated with corals may be indicative of the corals' health status and thus help guide restoration activities. Potential differences in microbiomes of restoration corals due to differences in host genetics, environmental condition, or geographic location, may then influence outplant success. The objective of the present study was to characterize and compare the microbiomes of apparently healthy Acropora cervicornis genotypes that were originally collected from environmentally distinct regions of Florida's Coral Reef and sampled after residing within Mote Marine Laboratory's in situ nursery near Looe Key, FL (USA) for multiple years. By using 16S rRNA high-throughput sequencing, we described the microbial communities of 74 A. cervicornis genotypes originating from the Lower Florida Keys (n = 40 genotypes), the Middle Florida Keys (n = 15 genotypes), and the Upper Florida Keys (n = 19 genotypes). Our findings demonstrated that the bacterial communities of A. cervicornis originating from the Lower Keys were significantly different from the bacterial communities of those originating from the Upper and Middle Keys even after these corals were held within the same common garden nursery for an average of 3.4 years. However, the bacterial communities of corals originating in the Upper Keys were not significantly different from those in the Middle Keys. The majority of the genotypes, regardless of collection region, were dominated by Alphaproteobacteria, namely an obligate intracellular parasite of the genus Ca. Aquarickettsia. Genotypes from the Upper and Middle Keys also had high relative abundances of Spirochaeta bacteria. Several genotypes originating from both the Lower and Upper Keys had lower abundances of Aquarickettsia, resulting in significantly higher species richness and diversity. Low abundance of Aquarickettsia has been previously identified as a signature of disease resistance. While the low-Aquarickettsia corals from both the Upper and Lower Keys had high abundances of an unclassified Proteobacteria, the genotypes in the Upper Keys were also dominated by Spirochaeta. The results of this study suggest that the abundance of Aquarickettsia and Spirochaeta may play an important role in distinguishing bacterial communities among A. cervicornis populations and compositional differences of these bacterial communities may be driven by regional processes that are influenced by both the environmental history and genetic relatedness of the host. Additionally, the high microbial diversity of low-Aquarickettsia genotypes may provide resilience to their hosts, and these genotypes may be a potential resource for restoration practices and management.