Electronic Cigarette Solvents, JUUL E-Liquids, and Biomarkers of Exposure: In Vivo Evidence for Acrolein and Glycidol in E-Cig-Derived Aerosols.

Despite the increasing popularity of e-cigarettes, their long-term health effects remain unknown. In animal models, exposure to e-cigarette has been reported to result in pulmonary and cardiovascular injury, and in humans, the acute use of e-cigarettes increases heart rate and blood pressure and induces endothelial dysfunction. In both animal models and humans, cardiovascular dysfunction associated with e-cigarettes has been linked to reactive aldehydes such as formaldehyde and acrolein generated in e-cigarette aerosols. These aldehydes are known products of heating and degradation of vegetable glycerin (VG) present in e-liquids. Here, we report that in mice, acute exposure to a mixture of propylene glycol:vegetable glycerin (PG:VG) or to e-cigarette-derived aerosols significantly increased the urinary excretion of acrolein and glycidol metabolites─3-hydroxypropylmercapturic acid (3HPMA) and 2,3-dihydroxypropylmercapturic acid (23HPMA)─as measured by UPLC-MS/MS. In humans, the use of e-cigarettes led to an increase in the urinary levels of 23HPMA but not 3HPMA. Acute exposure of mice to aerosols derived from PG:13C3-VG significantly increased the 13C3 enrichment of both urinary metabolites 13C3-3HPMA and 13C3-23HPMA. Our stable isotope tracing experiments provide further evidence that thermal decomposition of vegetable glycerin in the e-cigarette solvent leads to generation of acrolein and glycidol. This suggests that the adverse health effects of e-cigarettes may be attributable in part to these reactive compounds formed through the process of aerosolizing nicotine. Our findings also support the notion that 23HPMA, but not 3HPMA, may be a relatively specific biomarker of e-cigarette use.

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.

Establishing the Content Validity of a Modified Bank of School Anxiety Inventory Items for Use Among Adolescents With Chronic Pain.

OBJECTIVE: School anxiety is a prevalent mental health concern that drives school-related disability among youth with chronic pain. The only available measure of school anxiety-the School Anxiety Inventory, Short Version (SAI-SV)-lacks content specificity for measuring school anxiety in pediatric pain populations. We aimed to refine the SAI-SV by obtaining qualitative data about unique school situations that are anxiety-provoking for youth with pain and characterizing the nature of symptoms experienced in these situations. METHODS: Adolescents with chronic pain (n = 16) completed a semistructured interview focused on experiences with anxiety in school-related academic and social contexts. We employed thematic analysis to extend the empirical understanding of school anxiety from the perspective of patients suffering from pain and to generate new item content. The content was refined with iterative feedback from a separate group of adolescents with chronic pain (n = 5) and a team of expert pain psychologists (n = 3). RESULTS: We identified six themes within the data and generated new items designed to capture anxiety related to negative interactions with teachers and peers, falling behind with schoolwork, and struggles with concentration and fatigue. Participants and experts rated new item content as highly relevant for use among youth with pain. The updated item bank was named the School Anxiety Inventory for Chronic Pain. CONCLUSIONS: Future research is needed to complete the psychometric evaluation of the item bank and finalize items to be included in a measure that can be used in research and clinical settings. Implications for treating school-related anxiety among youth with pain are also discussed.

Electronic cigarette solvents, pulmonary irritation, and endothelial dysfunction: role of acetaldehyde and formaldehyde.

After more than a decade of electronic cigarette (E-cig) use in the United States, uncertainty persists regarding E-cig use and long-term cardiopulmonary disease risk. As all E-cigs use propylene glycol and vegetable glycerin (PG-VG) and generate abundant saturated aldehydes, mice were exposed by inhalation to PG-VG-derived aerosol, formaldehyde (FA), acetaldehyde (AA), or filtered air. Biomarkers of exposure and cardiopulmonary injury were monitored by mass spectrometry (urine metabolites), radiotelemetry (respiratory reflexes), isometric myography (aorta), and flow cytometry (blood markers). Acute PG-VG exposure significantly affected multiple biomarkers including pulmonary reflex (decreased respiratory rate, -50%), endothelium-dependent relaxation (-61.8 ± 4.2%), decreased WBC (-47 ± 7%), and, increased RBC (+6 ± 1%) and hemoglobin (+4 ± 1%) versus air control group. Notably, FA exposure recapitulated the prominent effects of PG-VG aerosol on pulmonary irritant reflex and endothelial dysfunction, whereas AA exposure did not. To attempt to link PG-VG exposure with FA or AA exposure, urinary formate and acetate levels were measured by GC-MS. Although neither FA nor AA exposure altered excretion of their primary metabolite, formate or acetate, respectively, compared with air-exposed controls, PG-VG aerosol exposure significantly increased post-exposure urinary acetate but not formate. These data suggest that E-cig use may increase cardiopulmonary disease risk independent of the presence of nicotine and/or flavorings. This study indicates that FA levels in tobacco product-derived aerosols should be regulated to levels that do not induce biomarkers of cardiopulmonary harm. There remains a need for reliable biomarkers of exposure to inhaled FA and AA.NEW & NOTEWORTHY Use of electronic cigarettes (E-cig) induces endothelial dysfunction (ED) in healthy humans, yet the specific constituents in E-cig aerosols that contribute to ED are unknown. Our study implicates formaldehyde that is formed in heating of E-cig solvents (propylene glycol, PG; vegetable glycerin, VG). Exposure to formaldehyde or PG-VG-derived aerosol alone stimulated ED in female mice. As ED was independent of nicotine and flavorants, these data reflect a "universal flaw" of E-cigs that use PG-VG.Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/e-cigarettes-aldehydes-and-endothelial-dysfunction/.

Exposure to volatile organic compounds - acrolein, 1,3-butadiene, and crotonaldehyde - is associated with vascular dysfunction.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Exposure to air pollution, specifically particulate matter of diameter ≤2.5 µm (PM2.5), is a well-established risk factor for CVD. However, the contribution of gaseous pollutant exposure to CVD risk is less clear. OBJECTIVE: To examine the vascular effects of exposure to individual volatile organic compounds (VOCs) and mixtures of VOCs. METHODS: We measured urinary metabolites of acrolein (CEMA and 3HPMA), 1,3-butadiene (DHBMA and MHBMA3), and crotonaldehyde (HPMMA) in 346 nonsmokers with varying levels of CVD risk. On the day of enrollment, we measured blood pressure (BP), reactive hyperemia index (RHI - a measure of endothelial function), and urinary levels of catecholamines and their metabolites. We used generalized linear models for evaluating the association between individual VOC metabolites and BP, RHI, and catecholamines, and we used Bayesian Kernel Machine Regression (BKMR) to assess exposure to VOC metabolite mixtures and BP. RESULTS: We found that the levels of 3HPMA were positively associated with systolic BP (0.98 mmHg per interquartile range (IQR) of 3HPMA; CI: 0.06, 1.91; P = 0.04). Stratified analysis revealed an increased association with systolic BP in Black participants despite lower levels of urinary 3HPMA. This association was independent of PM2.5 exposure and BP medications. BKMR analysis confirmed that 3HPMA was the major metabolite associated with higher BP in the presence of other metabolites. We also found that 3HPMA and DHBMA were associated with decreased endothelial function. For each IQR of 3HPMA or DHBMA, there was a -4.4% (CI: -7.2, -0.0; P = 0.03) and a -3.9% (CI: -9.4, -0.0; P = 0.04) difference in RHI, respectively. Although in the entire cohort the levels of several urinary VOC metabolites were weakly associated with urinary catecholamines and their metabolites, in Black participants, DHBMA levels showed strong associations with urinary norepinephrine and normetanephrine levels. DISCUSSION: Exposure to acrolein and 1,3-butadiene is associated with endothelial dysfunction and may contribute to elevated risk of hypertension in participants with increased sympathetic tone, particularly in Black individuals.

Acute and chronic vascular effects of inhaled crotonaldehyde in mice: Role of TRPA1.

Although crotonaldehyde (CR) is an abundant α,ß-unsaturated aldehyde in mainstream cigarette smoke (MCS), the cardiovascular toxicity of inhaled CR is largely unexplored. Thus, male C57BL/6 J mice were exposed acutely (1 h, 6 h, and 4d) and chronically (12 weeks) to CR (at levels relevant to MCS; 1 and 3 ppm), and cardiovascular and systemic outcomes were measured in vivo and in vitro. Diastolic blood pressure was decreased (hypotension) by both acute and chronic CR exposure. Vascular toxicity of inhaled CR was quantified in isolated aorta in response to agonists of contraction (phenylephrine, PE) and relaxation (acetylcholine, ACh; sodium nitroprusside, SNP). Although no change in contractility was observed, ACh-induced relaxations were augmented after both acute and chronic CR exposures whereas SNP-induced relaxation was enhanced only following 3 ppm CR exposure. Because CR is a known agonist of the transient receptor potential ankyrin 1 (TRPA1) channel, male TRPA1-null mice were exposed to air or CR (4d, 1 ppm) and aortic function assessed in vitro. CR exposure had no effect on TRPA1-null aortic function indicating a role of TRPA1 in CR effects in C57BL/6 J mice. Notably, CR exposure (4d, 1 ppm) had no effect on aortic function in female C57BL/6 J mice. This study shows that CR inhalation exposure induces real-time and persistent vascular changes that promote hypotension-a known risk factor for stroke. Because of continued widespread exposures of humans to combustion-derived CR (environmental and tobacco products), CR may be an important cardiovascular disease risk factor.

Tobacco Smoke and Endothelial Dysfunction: Role of Aldehydes?

PURPOSE OF REVIEW: Tobacco smoking is the most significant modifiable risk factor in the development of cardiovascular disease (CVD). Exposure to mainstream cigarette smoke (MCS) is associated with CVD through the development of endothelial dysfunction, a condition characterized by an imbalance of vasoactive factors in the vasculature. This dysfunction is thought to be induced in part by aldehydes generated at high levels in MCS. RECENT FINDINGS: Electronic cigarettes (e-cigs) may also pose CVD risk. Although the health effects of e-cigs are still largely unknown, the presence of aldehydes in e-cig aerosol suggests that e-cigs may induce adverse cardiovascular outcomes similar to those seen with MCS exposure. Herein, we review studies of traditional and emerging tobacco product use, shared harmful and potentially harmful constituents, and measures of biomarkers of harm (endothelial dysfunction) to examine a potential and distinct role of aldehydes in cardiovascular harm associated with cigarette and e-cig use.

Topical Review: Enhancing Understanding of the Clinical Meaningfulness of Outcomes to Assess Treatment Benefit from Psychological Therapies for Children with Chronic Pain.

OBJECTIVE: Despite the availability of measures for assessing physical, psychological, and health impact in children with chronic pain, there are not established guidelines for interpretation of children's pain outcomes following psychological treatment. The purpose of this topical review is to discuss clinical significance as a neglected area of consideration in pediatric chronic pain assessment and to make recommendations on how the field can move toward benchmarking on core outcome domains. METHOD: We review definitions of clinical significance and examples of several methodologies that have been used in other populations or are emerging in pediatric chronic pain including anchor-based methods, distribution-based methods, or multimethod approaches. RESULTS: Few measures across pediatric chronic pain outcome domains have established clinical significance of scores to interpret meaningful change following treatment limiting the interpretability of findings from clinical trials. In the context of clinical practice, several efforts to examine clinical significance to improve the translation of evidence-based measurement into standard clinical decision-making exist. CONCLUSIONS: Recommendations are provided to encourage additional validation efforts of outcome measures in pediatric chronic pain and to encourage authors to report clinical significance in clinical trials of psychological interventions for pediatric chronic pain.

Utility of the PROMIS Pediatric Pain Interference Scale in Juvenile Fibromyalgia.

OBJECTIVE: The current study tested the utility of the PROMIS Pediatric Pain Interference (PPI) in relation to the widely-used Functional Disability Inventory (FDI) in a small-scale clinical trial. METHODS: Forty youth with juvenile fibromyalgia (JFM) were randomized to either CBT only or a combined CBT and neuromuscular exercise group (i.e., FIT Teens). Participants completed the PPI and FDI at baseline, post-treatment, and three-month follow-up. RESULTS: The PPI and FDI were significantly correlated at baseline (r = .51) and post treatment (r = .53), and demonstrated similar improvements (d PPI = .87, d FDI = 1.22, p < .05) at post-treatment following FIT Teens. Following CBT only, neither the PPI nor the FDI improved significantly. CONCLUSIONS: The PPI may be appropriate for use in non-pharmacologic interventions for pediatric pain.

Risk Categorization Predicts Disability in Pain-associated Functional Gastrointestinal Disorders After 6 Months.

INTRODUCTION: For a large portion of youth, pain-associated functional gastrointestinal disorders (FGIDs) are associated with significant impairment over time. Clinically feasible methods to categorize youth with FGIDs at greatest risk for persistent pain-related impairment have not yet been identified. METHODS: Measures of functional disability, pain intensity, and anxiety were collected on 99 patients with FGIDs (ages 8-18) during a visit to a pediatric gastroenterology office to assess for the presence of risk. Follow-up data were obtained on a subset of this sample (n = 64) after 6 months, either in person or via mail. The present study examined whether a greater number of risk factors at baseline predicted greater pain-related disability at follow-up. RESULTS: Patients were divided into 4 groups based on number of risk factors present at the initial assessment: 0 (18.2%), 1 (24.2%), 2 (26.3%), and 3 (31.3%). The presence of 2 or 3 risk factors significantly predicted greater disability at follow-up compared to those with 0 risk factors (R = 0.311) and those with just 1 risk factor (Cohen's d values of -1.07 and -1.44, respectively). DISCUSSION: A simple approach to risk categorization can identify youth with FGIDs who are most likely to report increased levels of pain-related impairment over time. These findings have important clinical implications that support the utility of a brief screening process during medical care to inform referral for targeted treatment approaches to FGIDs.

2010 American College of Rheumatology Adult Fibromyalgia Criteria for Use in an Adolescent Female Population with Juvenile Fibromyalgia.

OBJECTIVES: To evaluate the utility of the 2010 American College of Rheumatology (ACR) adult fibromyalgia criteria for use in adolescents with juvenile fibromyalgia (JFM). STUDY DESIGN: Participants included 47 adolescent girls diagnosed with JFM (mean age = 15.3 years) and 48 age- and sex-matched adolescents (mean age = 15.0 years) with localized chronic pain (eg, headaches or abdominal pain). A trained examiner administered the Widespread Pain Index and Symptom Severity measures and also completed a manual tender point exam. Clinicians completed a form indicating the presence of active JFM per Yunus and Masi (1985) criteria, the only available and most commonly used measure for JFM. Criterion validity analysis was performed as well as t tests comparing symptoms between JFM and controls. RESULTS: With the Yunus and Masi criteria used as the gold standard, the 2010 ACR fibromyalgia criteria showed a sensitivity of 89.4% and specificity of 87.5%. CONCLUSION: The 2010 ACR measure appears to be a valuable tool for the identification of JFM. However, a slight modification to the 2010 ACR measure and inclusion of a clinical exam is recommended.

Anxiety Adversely Impacts Response to Cognitive Behavioral Therapy in Children with Chronic Pain.

OBJECTIVE: To evaluate whether clinical anxiety in children presenting to a pediatric pain management center is associated with a poorer treatment response for those who completed pain-focused cognitive behavioral therapy (CBT). STUDY DESIGN: The total sample consisted of 175 children, 40 of whom completed CBT for chronic pain. The Screen for Child Anxiety Related Emotional Disorders was completed at initial evaluation and outcome measures (average pain intensity and the Functional Disability Inventory) were collected during the initial evaluation and at the end of CBT. Group differences in outcomes were examined following CBT. The role of anxiety in CBT initiation and completion was also explored. RESULTS: Presence of clinical anxiety was associated with greater initiation and/or completion of pain-focused CBT but also a poorer treatment response. Specifically, the group with subclinical anxiety exhibited a substantial reduction in pain intensity, and the group with clinical anxiety exhibited a more limited response to treatment (F [1, 36] = 13.68 P < .01). A similar effect was observed for Functional Disability Inventory, such that the group with clinical anxiety had a significantly smaller response to treatment (F [1, 38] = 4.33 P < .05). The difference in pain and disability between groups following CBT suggest moderate effects (Cohen d = 0.77 and 0.78, respectively). CONCLUSIONS: Although youths with clinical anxiety are more likely to start and/or complete pain-focused CBT, anxiety has an adverse impact on CBT treatment response in children with chronic pain. Identification of patients with anxiety and use of tailored behavioral interventions may improve clinical outcomes.

Concordant parent-child reports of anxiety predict impairment in youth with functional abdominal pain.

BACKGROUND: Functional abdominal pain (FAP) is associated with significant anxiety and impairment. Prior investigations of child anxiety in youth with FAP are generally limited by small sample sizes, based on child report, and use lengthy diagnostic tools. It is unknown whether a brief anxiety-screening tool is feasible, whether parent and child reports of anxiety are congruent, and whether parent and child agreement of child anxiety corresponds to increased impairment. The purpose of this investigation was to examine anxiety characteristics in youth with FAP using parent and child reports. Parent-child agreement of child anxiety symptoms was examined in relation to pain and disability. METHODS: One hundred patients with FAP (8-18 years of age) recruited from pediatric gastroenterology clinics completed measures of pain intensity (Numeric Rating Scale) and disability (Functional Disability Inventory). Patients and caregivers both completed a measure of child anxiety characteristics (Screen for Child Anxiety and Related Disorders). RESULTS: Clinically significant anxiety symptoms were more commonly reported by youth (54%) than their parents (30%). Panic/somatic symptoms, generalized anxiety, and separation anxiety were most commonly endorsed by patients, whereas generalized anxiety, separation anxiety, and school avoidance were most commonly reported by parents. The majority (65%) of parents and children agreed on the presence (26%) or absence (39%) of clinically significant anxiety. Parent-child agreement of clinically significant anxiety was related to increased impairment. CONCLUSIONS: A brief screening instrument of parent and child reports of anxiety can provide clinically relevant information for comprehensive treatment planning in children with FAP.

Pain care for patients with epidermolysis bullosa: best care practice guidelines.

BACKGROUND: Inherited epidermolysis bullosa (EB) comprises a group of rare disorders that have multi-system effects and patients present with a number of both acute and chronic pain care needs. Effects on quality of life are substantial. Pain and itching are burdensome daily problems. Experience with, and knowledge of, the best pain and itch care for these patients is minimal. Evidence-based best care practice guidelines are needed to establish a base of knowledge and practice for practitioners of many disciplines to improve the quality of life for both adult and pediatric patients with EB. METHODS: The process was begun at the request of Dystrophic Epidermolysis Bullosa Research Association International (DEBRA International), an organization dedicated to improvement of care, research and dissemination of knowledge for EB patients worldwide. An international panel of experts in pain and palliative care who have extensive experience caring for patients with EB was assembled. Literature was reviewed and systematically evaluated. For areas of care without direct evidence, clinically relevant literature was assessed, and rounds of consensus building were conducted. The process involved a face-to-face consensus meeting that involved a family representative and methodologist, as well as the panel of clinical experts. During development, EB family input was obtained and the document was reviewed by a wide variety of experts representing several disciplines related to the care of patients with EB. RESULTS: The first evidence-based care guidelines for the care of pain in EB were produced. The guidelines are clinically relevant for care of patients of all subtypes and ages, and apply to practitioners of all disciplines involved in the care of patients with EB. When the evidence suggests that the diagnosis or treatment of painful conditions differs between adults and children, it will be so noted. CONCLUSIONS: Evidence-based care guidelines are a means of standardizing optimal care for EB patients, whose disease is often times horrific in its effects on quality of life, and whose care is resource-intensive and difficult. The guideline development process also highlighted areas for research in order to improve further the evidence base for future care.

Child pain catastrophizing mediates the relation between parent responses to pain and disability in youth with functional abdominal pain.

OBJECTIVES: Functional abdominal pain (FAP) in youth is associated with substantial impairment in functioning, and prior research has shown that overprotective parent responses can heighten impairment. Little is known about how a range of parental behaviors (overprotection, minimizing, and/or encouragement) in response to their child's pain interact with child coping characteristics (eg, catastrophizing) to influence functioning in youth with FAP. In this study, it was hypothesized that the relation between parenting factors and child disability would be mediated by children's levels of maladaptive coping (ie, pain catastrophizing). METHODS: Seventy-five patients with FAP presenting to a pediatric pain clinic and their caregivers participated in the study. Youth completed measures of pain intensity (Numeric Rating Scale), pain catastrophizing (Pain Catastrophizing Scale), and disability (Functional Disability Inventory). Caregivers completed measures of parent pain catastrophizing (Pain Catastrophizing Scale), and parent responses to child pain behaviors (Adult Responses to Child Symptoms: Protection, Minimizing, and Encouragement/Monitoring subscales). RESULTS: Increased functional disability was significantly related to higher child pain intensity, increased child and parent pain catastrophizing, and higher levels of encouragement/monitoring and protection. Parent minimization was not related to disability. Child pain catastrophizing fully mediated the relation between parent encouragement/monitoring and disability and partially mediated the relation between parent protectiveness and disability. CONCLUSIONS: The impact of parenting behaviors in response to FAP on child disability is determined, in part, by the child's coping style. Findings highlight a more nuanced understanding of the parent-child interaction in determining pain-related disability levels, which should be taken into consideration in assessing and treating youth with FAP.

Formaldehyde and the transient receptor potential ankyrin-1 contribute to electronic cigarette aerosol-induced endothelial dysfunction in mice.

Electronic nicotine delivery systems (ENDS) aerosol exposures can induce endothelial dysfunction (ED) in healthy young humans and animals. Thermal degradation of ENDS solvents, propylene glycol, and vegetable glycerin (PG: VG), generates abundant formaldehyde (FA) and other carbonyls. Because FA can activate the transient receptor potential ankyrin-1 (TRPA1) sensor, we hypothesized that FA in ENDS aerosols provokes TRPA1-mediated changes that include ED and "respiratory braking"-biomarkers of harm. To test this, wild-type (WT) and TRPA1-null mice were exposed by inhalation to either filtered air, PG: VG-derived aerosol, or FA (5 ppm). Short-term exposures to PG: VG and FA-induced ED in female WT but not in female TRPA1-null mice. Moreover, acute exposures to PG: VG and FA stimulated respiratory braking in WT but not in TRPA1-null female mice. Urinary metabolites of FA (ie, N-1,3-thiazolidine-4-carboxylic acid, TCA; N-1,3-thiazolidine-4-carbonyl glycine, TCG) and monoamines were measured by LC-MS/MS. PG: VG and FA exposures significantly increased urinary excretion of both TCA and TCG in both WT and TRPA1-null mice. To confirm that inhaled FA directly contributed to urinary TCA, mice were exposed to isotopic 13C-FA gas (1 ppm, 6 h). 13C-FA exposure significantly increased the urine level of 13C-TCA in the early collection (0 to 3 h) supporting a direct relationship between inhaled FA and TCA. Collectively, these data suggest that ENDS use may increase CVD risk dependent on FA, TRPA1, and catecholamines, yet independently of either nicotine or flavorants. This study supports that levels of FA in ENDS-derived aerosols should be lowered to mitigate CVD risk in people who use ENDS.

Cognitive behavioral therapy for the treatment of juvenile fibromyalgia: a multisite, single-blind, randomized, controlled clinical trial.

OBJECTIVE: Juvenile fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain disorder in children and adolescents for which there are no evidence-based treatments. The objective of this multisite, single-blind, randomized clinical trial was to test whether cognitive-behavioral therapy (CBT) was superior to fibromyalgia (FM) education in reducing functional disability, pain, and symptoms of depression in juvenile FMS. METHODS: Participants were 114 adolescents (ages 11-18 years) with juvenile FMS. After receiving stable medications for 8 weeks, patients were randomized to either CBT or FM education and received 8 weekly individual sessions with a therapist and 2 booster sessions. Assessments were conducted at baseline, immediately following the 8-week treatment phase, and at 6-month followup. RESULTS: The majority of patients (87.7%) completed the trial per protocol. Intent-to-treat analyses showed that patients in both groups had significant reductions in functional disability, pain, and symptoms of depression at the end of the study, and CBT was significantly superior to FM education in reducing the primary outcome of functional disability (mean baseline to end-of-treatment difference between groups 5.39 [95% confidence interval 1.57, 9.22]). Reduction in symptoms of depression was clinically significant for both groups, with mean scores in the range of normal/nondepressed by the end of the study. Reduction in pain was not clinically significant for either group (<30% decrease in pain). There were no study-related adverse events. CONCLUSION: In this controlled trial, CBT was found to be a safe and effective treatment for reducing functional disability and symptoms of depression in adolescents with juvenile FMS.

Importance of addressing anxiety in youth with functional abdominal pain: suggested guidelines for physicians.

Functional abdominal pain (FAP) is a common pediatric disorder associated with impairment in functioning that may persist for the long term. Anxiety is common in youth with FAP, and may be an important factor in predicting youth who are at greatest risk for increased impairment because of pain symptoms. In this article, we examine the relation between anxiety and impairment in youth with FAP. Furthermore, we explore various biopsychosocial factors (eg, neurobiological substrates, coping strategies, social factors) that may be implicated in the relation among FAP, anxiety, and increased impairment. Finally, we propose physician guidelines for screening and treatment of youth with FAP and co-occurring anxiety. Youth with FAP and co-occurring anxiety may benefit from cognitive-behavioral therapy in the context of multidisciplinary care.

A survey of conventional and complementary therapies used by youth with juvenile-onset fibromyalgia.

Little is known regarding treatment choices of youth diagnosed with juvenile-onset fibromyalgia (JFM) as they move into young adulthood. Additionally, there is little empirical evidence to guide youth with FM into appropriate treatment options, leading to a variety of therapies used to manage FM symptoms. The purpose of this descriptive study was to examine all therapies used by individuals with JFM as they entered young adulthood and the perceived effectiveness of these treatments. As part of a larger follow-up study, participants completed a web-based survey of all current and past treatments received for FM symptoms 2 years after their initial presentation and diagnosis at a pediatric rheumatology clinic. One hundred ten out of 118 eligible patients participated in the follow-up assessment as young adults (mean age 18.97 years; 93.6% female). A majority of participants reported use of conventional medications (e.g., antidepressants, anticonvulsants) and nondrug therapies (e.g., psychotherapy). Currently and within the past 2 years, antidepressant medications were the most commonly used to manage FM. Complementary treatments were used less often, with massage being the most popular choice. Although currently used treatments were reported as being effective, past treatments, especially medications, were viewed as being more variably effective. This is a potential reason why young adults with JFM might try more complementary and alternative approaches to managing their symptoms. More controlled studies are needed to investigate the effectiveness of these complementary methods to assist treatment providers in giving evidence-based treatment recommendations.

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.