Psychological interventions for individuals with Ehlers-Danlos syndrome and hypermobility spectrum disorder: a scoping review.

PURPOSE: To identify the nature and extent of the evidence on psychological interventions among individuals with Ehlers-Danlos Syndrome (EDS) and Hypermobility Spectrum Disorder (HSD). MATERIALS AND METHODS: Eligible studies reported on psychological interventions for individuals of all ages with EDS and/or HSD. All studies published in English were included, with no restrictions to publication year or status. MEDLINE, CINAHL, EMBASE, and PsycINFO were searched. Two reviewers independently screened studies and abstracted data. RESULTS: This scoping review included 10 studies reporting on EDS, HSD, or both. Only cohort studies and case studies were identified. Four studies investigated Cognitive Behavioural Therapy (CBT), one investigated Dialectical Behavioural Therapy (DBT), two investigated psychoeducation, two investigated Intensive Interdisciplinary Pain Treatment (IIPT), and one investigated Acceptance Commitment Therapy (ACT). Interventions targeted pain management, self-destructive behaviours, and related psychological issues (e.g., depression/anxiety). Sample sizes were small (n < 50) for most studies and interventions were generally poorly described. CONCLUSIONS: There is a critical need for high-quality research surrounding psychological interventions for individuals with EDS/HSD. Psychological interventions for these individuals are understudied and existing studies lack validity. Researchers should investigate psychological interventions for individuals with all types of EDS/HSD with high-quality studies to validate findings from the existing studies.

Impact of Sleep Disturbance on Fatigue, Nausea, and Pain: Mediating Role of Depressive Symptoms Among Youth With Disorders of Gut-Brain Interaction.

OBJECTIVES: A high degree of sleep disturbance is reported among youth with disorders of gut-brain interaction (DGBIs). Given that sleep quality impacts a range of pediatric health outcomes including somatic sensations (eg, pain) and depressive mood occurs relatively frequently among youth with DGBIs, there is a dire need to disentangle the unique contributions of sleep and depressive mood on the somatic sensations experienced by youth with DGBIs. We aimed to examine whether depressive mood mediates the relations among sleep disturbance and pain intensity, nausea, and fatigue among youth with DGBIs. METHODS: One hundred eighteen patients aged 8-17 years ( Mage = 14.05, SD = 2.88; 70.34% female), 83.05% White/non-Hispanic recruited at a pediatric neurogastroenterology clinic completed measures of sleep disturbance, nausea, fatigue, pain intensity, and depressive mood. Three mediation models examined the effect of sleep disturbance on nausea, fatigue, and pain, with depressive mood as a mediator. RESULTS: Participants reported moderate sleep disturbance. Depressive mood partially mediated the significant, respective relations between greater sleep disturbance and more severe nausea and fatigue. Sleep disturbance was significantly associated with higher pain intensity; however, depressive mood was not a significant mediator of this relation. CONCLUSIONS: Sleep quality is a major concern among youth with DGBIs. Low sleep quality may worsen nausea and fatigue via co-occurring increases in depressive mood symptoms. In contrast, sleep disturbance may directly increase pain, regardless of youths' depressive mood symptoms. Future research should explore these relations through prospective studies leveraging a combination of subjective and objective assessment approaches.

Salivary cortisol levels and appraisals of daily hassles across dimensions of the tripartite model of anxiety and depression in emerging adults.

The objective of this study was to investigate how cortisol levels and appraisals of daily hassles differ across tripartite dimensions of depression and anxiety in emerging adults. Data collected from a sample of undergraduate students at a large Midwestern university was used to investigate these aims. This included salivary cortisol data collected over four days, scores on a measure of the tripartite model of anxiety and depression, and scores on a measure of daily hassles administered everyday for two weeks. Generalized estimating equations and multilevel modeling techniques were used to analyze data. Elevated cortisol levels during the awakening period and the evening period, lower total levels across the day, steeper diurnal slopes, and elevated levels of negative affect and physiological hyperarousal predicted experiences of daily hassles. Tripartite dimensions were unrelated to cortisol indices. The present study demonstrates the utility of modeling multiple cortisol indices and provides evidence of differential associations between physiological and phenomenological indices of stress.

Obstetrical and neonatal outcomes of cardio-facio-cutaneous syndrome: Prenatal consequences of Ras/MAPK dysregulation.

We systematically delineated the prenatal phenotype, and obstetrical and neonatal outcomes of the RASopathy cardio-facio-cutaneous (CFC) syndrome. A comprehensive, retrospective medical history survey was distributed to parents of children with confirmed CFC in collaboration with CFC International, Inc. Data were collected on CFC gene variant, maternal characteristics, pregnancy course, delivery, and neonatal outcomes with the support of medical records. We identified 43 individuals with pathogenic variants in BRAF (81%), MEK1 (14%), or MEK2 (5%) genes. The median age was 8.5 years. Hyperemesis gravidarum, gestational diabetes, gestational hypertension, and preeclampsia occurred in 5/43 (12%), 4/43 (9%), 3/43 (7%), and 3/43 (7%) of pregnancies, respectively. Second and third trimester ultrasound abnormalities included polyhydramnios, macrocephaly, macrosomia, and renal and cardiac abnormalities. Delivery occurred via spontaneous vaginal, operative vaginal, or cesarean delivery in 15/42 (36%), 7/42 (16%), and 20/42 (48%), respectively. Median gestational age at delivery was 37 weeks and median birth weight was 3501 grams. Germline pathogenic vaiants had mutiple congenital consequences including polyhydramnios, renal and cardiac abnormalities, macrosomia, and macrocephaly on second and third trimester ultrasound. Elevated rates of operative delivery and neonatal complications were also noted. Understanding and defining a prenatal phenotype may improve prenatal prognostic counseling and outcomes.

A Multimodal Intervention for Reducing Unnecessary Repeat Glycated Hemoglobin Testing.

OBJECTIVES: Reducing unnecessary tests that do not enhance quality can promote health-care value. Glycated hemoglobin (A1C) is often ordered at a frequency exceeding the recommendation of once every 3 months. We conducted a quality improvement (QI) initiative aimed to reduce unnecessary repeat testing by 75% at a tertiary care academic hospital. METHODS: A retrospective baseline analysis was conducted on laboratory data from 2019 that enumerated unnecessary A1C tests, defined as repeat tests ordered within 60 days. A multifaceted change intervention with iterative plan-do-study-act cycles was introduced in March 2019 to educate providers and to automatically cancel A1C tests requested within 60 days. Monthly totals of A1C testing processed were plotted on statistical process control charts. RESULTS: In 2019, 11% of all A1C tests ordered were unnecessary. Between March 2020 and January 2021, 11% of the tests (N=14,247 tests) were unnecessary, of which 84% were cancelled with our intervention. Providers in cardiology and nephrology accounted for over half (55%) of the unnecessary tests ordered. CONCLUSIONS: A 2-pronged approach informed by root-cause analysis, and comprised of gatekeeping and provider education, can effectively promote resource stewardship for reducing unnecessary A1C testing.

The role of functional disability and social support in psychological outcomes for individuals with pediatric hypermobile ehlers-danlos syndrome.

Hypermobile Ehlers-Danlos syndrome (hEDS) includes physical symptoms of chronic pain, fatigue, gastrointestinal dysfunction, and joint subluxations/dislocations. This study aims to fill a research gap regarding the psychosocial well-being in pediatric hEDS by assessing relationships between functional disability, social support, and mental health. Increased functional disability is hypothesized to be associated with increased mental health challenges, specifically anxiety and depression, and general social support is hypothesized to moderate this relationship, such that higher perceived social support will mitigate the negative psychological impacts of functional disability. Gender's influence on mental health in pediatric hEDS is also explored. Thirty-four youth with pediatric hEDS recruited from a United States Midwest multidisciplinary genetics clinic completed self-report questionnaires. Results demonstrate associations between functional disability and mental health, and social support and mental health independently; however, moderation was not found. Functional disability and social support each have a unique influence on the mental health of children with pediatric hEDS and should each receive clinical attention. Exploratory analyses into the influence of gender provide a groundwork for future studies.

Silver-loaded mesoporous silica nanoparticles enhanced the mechanical and antimicrobial properties of 3D printed denture base resin.

The aim of this study is to develop a novel 3D printed denture base resin material modified with mesoporous silica nanocarrier loaded with silver (Ag/MSN) to enhance mechanical and antimicrobial properties. Acrylate resin-based was incorporated with various proportion of Ag/MSN (0.0-2.0 wt%). Specimens with different geometry were printed and characterized accordingly for the effect of modification on properties such as: mechanical and physical properties, chemical composition and degree of conversion, as well as biological response in term of biocompatibility and antimicrobial against oral fibroblast and candida biofilm (C. albicans), respectively. The consecutive addition of Ag/MSN improved significantly surface hardness and crack propagation resistance, while flexural strength remained similar to control; however, a negligible decrease was observed with higher concentrations ≥1 wt%. No significant difference was noticed with water sorption, while water solubility had a remarkable trend of reduction associated with filler content. The surface roughness significantly increased when concentration of Ag/MSN was ≥1.0 wt%. A significant reduction in C. albicans biofilm mass, as the inhibition proficiency was correlated with the proportion of the filler. With respect to the amount of Ag/MSN, the modification was compatible toward fibroblast cells. The sequential addition of Ag/MSN enhanced significantly the mechanical and antimicrobial properties of the 3D printed resin-based material without affecting adversely compatibility. The acrylic resin denture base material has susceptibility of microbial adhesion which limits its application. Silver loaded MSN showed a significant performance to enhance antimicrobial activity against C. albicans which is the main cause of denture stomatitis. The proposed invention is a promise technique for clinical application to provide an advanced prosthesis fabrication and serve as long-term drug delivery.

Comparison of pain and psychosocial correlates among Hispanic and Non-Hispanic White youth with chronic pain.

Introduction: Despite well-documented pain disparities among adults from non-White and Hispanic groups, less is known about pain disparities in non-White and Hispanic pediatric populations. Objectives: We compare pain and related psychosocial factors at the individual (pain intensity, pain interference, pain catastrophizing, co-occurring symptoms), social (peer relations), and systemic (health insurance) levels among Hispanic and Non-Hispanic White (NHW) youth with chronic pain. Methods: Eight hundred thirty-seven (71.4% female) Hispanic (n = 268, 32%) and NHW (n = 569, 68%) youth ages 8 to 17 years (M = 14.00; SD = 2.54) completed a survey at their initial visit to a pain clinic. Independent sample t tests investigated mean differences in psychosocial factors at the individual and social levels. Chi-squared tests investigated differences at the systemic level. Bivariate correlations for each group were compared using Fisher r-to-z transformations. Results: Hispanic youth reported higher levels of pain intensity (t[811] = -2.75, P = 0.006). Groups did not differ in reports of other individual or social factors. Non-Hispanic White youth were more likely to have private insurance (OR, 5.66). All examined variables were significantly correlated among NHW youth. Correlations were weaker or nonsignificant among Hispanic youth. Fisher r-to-z transformations revealed these group differences to be significant. Conclusion: Hispanic youth report higher pain levels than NHW counterparts and lower likelihood of having private insurance. Pain and psychosocial factors correlate differently among the 2 groups highlighting a need to better understand the chronic pain experiences of diverse youth because models derived primarily from NHW populations may not generalize across ethnic and racial groups.

Healthcare utilization among youth with Ehlers-Danlos syndrome hypermobile type.

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

Using Technology to Assess Bidirectionality between Daily Pain and Physical Activity: The Role of Marginalization during Emerging Adulthood.

Emerging adulthood is often overlooked as a developmental time period critical to shaping future health outcomes. Recurrent pain is a commonly experienced health concern within this age group, particularly headaches and low back pain, and early experiences of recurrent pain are related to subsequent chronic pain and disability. Furthermore, adults from marginalized populations report more frequent and severe recurrent pain. Many studies have demonstrated the therapeutic effect of physical activity on pain relief; however, others have demonstrated that physical activity can also exacerbate pain symptoms. Therefore, the current study aimed to (1) assess a bidirectional relationship between reported pain and engagement in physical activity among an emerging adult sample (N = 265) and (2) determine whether sociodemographic factors moderate this relationship. Using longitudinal daily reported pain and ActiGraph monitor data collected over two weeks, a novel dynamic structural equation modeling approach was employed. Results indicated no significant cross-lagged relationships between pain and physical activity, and no significant moderation effects. These findings suggest that a bidirectional relationship does not exist among a diverse college sample of emerging adults even after considering sociodemographic moderators. Excellent retention and few missing data suggest that using accelerometers and daily diaries are feasible methods to collect data in this population. Sample considerations and future analytical approaches are discussed.

The Relationship between Stressors and Pain-Related Clinical Outcomes in Pediatric Chronic Pain Patients.

Youth with chronic pain and youth who have experienced stressors are at risk for poor outcomes; however, little is known about the intersection of pain and stressors. This study aims to understand the prevalence of stressors among youth with chronic pain and the relationship between stressors and pain-related outcomes. Seven hundred and seventy youth with chronic pain aged 8-18 (Mage = 14.15 years, 70% female) reported pain characteristics, stressors, anxiety, disability, and quality of life. Most participants (82%) endorsed at least one stressor. A greater number of stressors was significantly related to greater anxiety and disability, and lower levels of quality of life. School stressors were significantly associated with functional disability; family, school, and peer stressors were significantly associated with anxiety and quality of life. Stressors are common in youth with chronic pain, and the presence of stressors is related to greater functional impairment. The results of this preliminary study using semi-structured clinical interviews suggest the importance of developing a validated measure that encompasses a wide variety of stressors for youth with pain. Future research on patient-reported stressors, relative intensity, and impact are needed.

Hassles predict physical health complaints in undergraduate students: a dynamic structural equation model analysis of daily diary data.

OBJECTIVE: Daily hassles and physical health complaints are common among undergraduate students, and both are related to negative academic and psychosocial outcomes. However, the extent to which hassles or health complaints persist from day to day is underexplored, and studies examining whether hassles predict health complaints or vice versa, are lacking. This study aimed to examine the temporal stability and to define the temporal relationship between daily hassles and health symptoms in undergraduate students. DESIGN: Participants (n = 255, mean age = 19.2 years, 69% female, 53% White) completed 14 consecutive daily diaries of hassles and health complaints. MAIN OUTCOME MEASURES: Daily reports of the Brief College Students Hassles Scale and the Patient Health Questionnaire-15. RESULTS: Hassles and health complaints demonstrated stability through autocorrelations. Hassles significantly predicted subsequent health complaints, but health complaints did not significantly predict subsequent hassles. However, the two paths did not differ significantly. CONCLUSION: Students reporting elevations in one or both domains may benefit from interventions aimed at reducing daily hassles, in order to promote better perceived health and well-being.

Systematic evaluation of commercially available pain management apps examining behavior change techniques.

ABSTRACT: Mobile health (mHealth) apps have the potential to enhance pain management through the use of daily diaries, medication and appointment reminders, education, and facilitating communication between patients and providers. Although many pain management apps exist, the extent to which these apps use evidence-based behavior change techniques (BCTs) remains largely unknown, making it nearly impossible for providers to recommend apps with evidence-based strategies. This study systematically evaluated commercially available pain management apps for evidence-based BCTs and app quality. Pain management apps were identified using the search terms "pain" and "pain management" in the App and Google Play stores. Reviewed apps were specific to pain management, in English, for patients, and free. A total of 28 apps were coded using the taxonomy of BCTs. App quality was assessed using the Mobile App Rating Scale. Apps included 2 to 15 BCTs (M = 7.36) and 1 to 8 (M = 4.21) pain management-specific BCTs. Prompt intention formation, instruction, behavioral-health link, consequences, feedback, and self-monitoring were the most common BCTs used in the reviewed apps. App quality from the Mobile App Rating Scale ranged from 2.27 to 4.54 (M = 3.65) out of a possible 5, with higher scores indicating better quality. PainScale followed by Migraine Buddy demonstrated the highest number of overall and pain management BCTs as well as good quality scores. Although existing apps should be assessed through randomized controlled trials and future apps should include capabilities for electronic medical record integration, current pain management apps often use evidence-based pain management BCTs.

Pain Symptomatology and Management in Pediatric Ehlers-Danlos Syndrome: A Review.

Ehlers-Danlos syndromes (EDS) are a group of connective tissue disorders that manifest with hyperextensibility of joints and skin, and general tissue fragility. While not a major criterion for clinical diagnosis, pain is a frequently endorsed symptom across subtypes of EDS. As such, the present review aims to summarize research to date on pain characteristics and management, and the relationship between such pain symptomatology and quality of life in pediatric EDS. Characteristics of pain, including theorized etiology, relative intensity and extent of pain are described, as well as descriptions of frequently endorsed pain sites (musculoskeletal, and non-musculoskeletal). Interventions related to the management of musculoskeletal (e.g., pharmaceutical intervention, physical therapy) and non-musculoskeletal pain (e.g., pharmaceutical and psychological interventions) are discussed, highlighting the need for additional research related to pediatric pain management in the context of hypermobility syndromes. In addition, the relationship between pain in pediatric EDS and quality of life is described. Finally, limitations of literature to date are described and recommendations for future lines of research are outlined.

Sociodemographic and Environmental Factors are Associated with Adolescents' Pain and Longitudinal Health Outcomes.

Research in adult populations indicates that several sociodemographic and environmental variables increase risk for pain and poor outcomes. There is little research exploring the impact of household income, health insurance coverage, barriers to health care, neighborhood and school safety, violence experienced, and neighborhood isolation on pediatric chronic pain. Data from the Add Health Study, a longitudinal examination of a nationally-representative adolescent sample were analyzed. The relationships between demographic variables, risk factors, chronic pain, and long-term health outcomes were examined. Adolescents with chronic pain had lower income, more health care barriers, greater safety concerns, and experienced more violence compared to those without pain. In a model together, female sex, White race/ethnicity, and greater health care barriers, safety concerns, and violence exposure conferred significant risk for chronic pain. Additional analyses revealed nuances in the strength of risk factors between racial/ethnic groups. Systemic health care barriers were significantly associated with chronic pain and may delay symptom alleviation and return to functioning. Considering access to care is necessary in prevention efforts. Among adolescents with chronic pain, greater safety concerns predicted poor mental health outcomes, particularly for White females. The cumulative stress of environmental concerns, such as safety, and managing chronic pain may worsen functioning. PERSPECTIVE: Adolescents with chronic pain had lower income, and more health care barriers, safety concerns, and violence exposure compared to those without chronic pain. Access to care is a significant problem in youth with chronic pain. The relationships between race/ethnicity, risk factors, and health outcomes are complex and require additional research.

Symptom complaints and impact on functioning in youth with hypermobile Ehlers-Danlos syndrome.

Hypermobile Ehlers-Danlos syndrome (hEDS), a genetic connective tissue disorder, involves several body systems which makes symptom management and functioning difficult. The aim of this study was to understand pediatric hEDS patients' symptoms and primary complaints. Additionally, we examined the cumulative impact of symptoms on physical and psychological functioning. Thirty-four youth with hEDS were recruited from a genetics clinic and reported the hardest thing about having hEDS, their pain, fatigue, physical symptoms, functional disability, anxiety, and depression. Physical symptoms (pain and fatigue) and limitations (keeping up with friends) were reported as the most difficult parts of having hEDS. A higher number of somatic symptoms was the strongest predictor of disability, anxiety, and depression. Physical symptoms are subjectively distressing and significantly related to impairments in physical and psychological functioning. Thus, addressing these varied symptoms in treatment may yield better functioning in youth with hEDS.

Long-term outcomes of adolescents with juvenile-onset fibromyalgia into adulthood and impact of depressive symptoms on functioning over time.

Juvenile-onset fibromyalgia (JFM) is typically diagnosed in adolescence and characterized by widespread pain and marked functional impairment. The long-term impact of JFM into adulthood is poorly understood. The objectives of this study were to describe physical and psychosocial outcomes of youth diagnosed with JFM in early adulthood (∼8-year follow-up), examine longitudinal trajectories of pain and depressive symptoms from adolescence to young adulthood, and examine the impact of pain and depressive symptoms on physical functioning over time. Participants were 97 youth with JFM enrolled in a prospective longitudinal study in which pain symptoms, and physical and psychosocial functioning were assessed at 4 time points over approximately 8 years. At the time 4 follow-up (Mage = 24.2 years), the majority continued to suffer from pain and impairment in physical, social, and psychological domains. However, trajectories of pain and emotional symptoms showed varying patterns. Longitudinal analysis using growth mixture modeling revealed 2 pain trajectories (Steady Improvement and Rapid Rebounding Improvement), whereas depressive symptoms followed 3 distinct trajectories (Low-Stable, Improving, and Worsening). Membership in the Worsening Depressive symptoms group was associated with poorer physical functioning over time (P < 0.001) compared with the Low-Stable and Improving groups. This study offers evidence that although JFM symptoms persist for most individuals, pain severity tends to decrease over time. However, depressive symptoms follow distinct trajectories that indicate subgroups of JFM. In particular, JFM patients with worsening depressive symptoms showed decreasing physical functioning and may require more intensive and consistent intervention to prevent long-term disability.

Clinical Reference Points for the Screen for Child Anxiety-related Disorders in 2 Investigations of Youth With Chronic Pain.

OBJECTIVE: Anxiety is common in pediatric chronic pain and is related to a higher risk for poor outcomes; thus, there is a need for effective clinical screening methods to identify youth with chronic pain and co-occurring anxiety. The Screen for Child Anxiety-related Disorders (SCARED) is a validated measure that defines clinically significant anxiety using the traditional clinical cut-off, but in pain populations, may fail to screen in youth with subclinical anxiety that may also be at increased risk. Two studies aimed to devise a clinically meaningful approach to capture anxiety severity in pediatric chronic pain. MATERIALS AND METHODS: Study 1 (n=959) and Study 2 (n=207) were completed at 2 separate pediatric pain clinics, where the SCARED was administered along with measures of disability, activity limitations, pain intensity, quality of life, and pain catastrophizing. Groups with different levels of anxiety were compared on clinical outcomes via multivariate analyses of variance or independent samples t tests. RESULTS: A tertile solution suggested the following anxiety groupings based on the SCARED: minimal (0 to 12), subclinical (13 to 24), and clinical (≥25). Across both studies, the tertile solution was generally superior in classifying different levels of pain-related outcomes. DISCUSSION: Future directions include testing the utility of this anxiety classification system to identify youth with subclinical levels of anxiety for early intervention focused on both pain and anxiety management.