Beyond intent to treat (ITT): A complier average causal effect (CACE) estimation primer.

Randomized control trials (RCTs) have long been the gold standard for allowing causal inferences to be made regarding the efficacy of a treatment under investigation, but traditional RCT data analysis perspectives do not take into account a common reality: imperfect participant compliance to treatment. Recent advances in both maximum likelihood parameter estimation and mixture modeling methodology have enabled treatment effects to be estimated, in the presence of less than ideal levels of participant compliance, via a Complier Average Causal Effect (CACE) structural equation mixture model. CACE is described in contrast to "intent to treat" (ITT), "per protocol", and "as treated" RCT data analysis perspectives. CACE model assumptions, specification, estimation, and interpretation will all be demonstrated with simulated data generated from a randomized controlled trial of cognitive-behavioral therapy for Juvenile Fibromyalgia. CACE analysis model figures, linear model equations, and Mplus estimation syntax examples are all provided. Data needed to reproduce analyses in this article are available as supplemental materials (online only) in the Appendix of this article.

A Qualitative Examination of a New Combined Cognitive-Behavioral and Neuromuscular Training Intervention for Juvenile Fibromyalgia.

OBJECTIVES: Adolescents with juvenile fibromyalgia (JFM) are typically sedentary despite recommendations for physical exercise, a key component of pain management. Interventions such as cognitive-behavior therapy (CBT) are beneficial but do not improve exercise participation. The objective of this study was to obtain preliminary information about the feasibility, safety, and acceptability of a new intervention--Fibromyalgia Integrative Training for Teens (FIT Teens), which combines CBT with specialized neuromuscular exercise training modified from evidence-based injury prevention protocols. MATERIALS AND METHODS: Participants were 17 adolescent females (aged 12 to 18 y) with JFM. Of these, 11 completed the 8-week (16 sessions) FIT Teens program in a small-group format with 3 to 4 patients per group. Patients provided detailed qualitative feedback via individual semistructured interviews after treatment. Interview content was coded using thematic analysis. Interventionist feedback about treatment implementation was also obtained. RESULTS: The intervention was found to be feasible, well tolerated, and safe for JFM patients. Barriers to enrollment (50% of those approached) included difficulties with transportation or time conflicts. Treatment completers enjoyed the group format and reported increased self-efficacy, strength, and motivation to exercise. Participants also reported decreased pain and increased energy levels. Feedback from participants and interventionists was incorporated into a final treatment manual to be used in a future trial. DISCUSSION: Results of this study provided initial support for the new FIT Teens program. An integrative strategy of combining pain coping skills via CBT enhanced with tailored exercise specifically designed to improve confidence in movement and improving activity participation holds promise in the management of JFM.

Psychiatric Disorders in Young Adults Diagnosed with Juvenile Fibromyalgia in Adolescence.

OBJECTIVE: Adolescents with juvenile-onset fibromyalgia (JFM) have increased rates of psychiatric disorders, but to our knowledge no studies have examined psychiatric disorders in adolescents with JFM when they enter young adulthood. This study examined the prevalence of psychiatric disorders in young adults diagnosed with JFM during adolescence and the relationship between mental health diagnoses and physical functioning. METHODS: Ninety-one young adults (mean age 21.60, SD 1.96) with a history of JFM being followed as part of a prospective longitudinal study and 30 matched healthy controls (mean age 21.57, SD 1.55) completed a structured interview of psychiatric diagnoses and a self-report measure of physical impairment. RESULTS: Young adults with a history of JFM were more likely to have current and lifetime histories of anxiety disorders (70.3% and 76.9%, respectively) compared with controls (33.3% for both, both p < 0.001). Individuals with JFM were also more likely to have current and lifetime histories of major mood disorders (29.7% and 76.9%, respectively) compared with controls (10% and 40%, p < 0.05). The presence of a current major mood disorder was significantly related to impairment in physical functioning [F (1, 89) = 8.30, p < 0.01] and role limitations attributable to a physical condition [F (1, 89) = 7.09, p < 0.01]. CONCLUSION: Psychiatric disorders are prevalent in young adulthood for individuals with a history of JFM, and a current major mood disorder is associated with greater physical impairment. Greater attention to early identification and treatment of mood disorders in patients with JFM is warranted.

Preliminary evidence of altered biomechanics in adolescents with juvenile fibromyalgia.

OBJECTIVE: Juvenile fibromyalgia (FM) is characterized by chronic musculoskeletal pain and marked reduction in physical activity. Despite recommendations for exercise to manage juvenile FM pain, exercise adherence is poor. Because of pain and activity avoidance, adolescents with juvenile FM are at risk for altered joint mechanics that may make them susceptible to increased pain and reduced tolerance for exercise. The primary aim of this study was to assess functional deficits in patients with juvenile FM compared to healthy controls using objective biomechanical assessment. METHODS: Female adolescent patients with juvenile FM (n = 17) and healthy controls (n = 14) completed biomechanical assessments, including gait analysis and tests of lower extremity strength (isokinetic knee extension/flexion and hip abduction) and functional performance (drop vertical jump test) along with self-reported measures of disability (Functional Disability Inventory), pain intensity, depressive symptoms (Children's Depression Inventory), and fear of movement (Tampa Scale of Kinesiophobia). RESULTS: Patients with juvenile FM demonstrated mild deficiencies in walking gait and functional performance (P < 0.05 for both) and significantly lower left knee extension and flexion strength (18-22% deficit) and bilateral hip abduction strength (34-38%) compared with healthy controls (P < 0.008 for all). Patients with juvenile FM reported significantly higher functional disability, pain intensity, depressive symptoms, and fear of movement relative to controls (P < 0.01 for all). CONCLUSION: This study showed that adolescents with juvenile FM exhibited objective alterations in biomechanics and self-reported fear of movement that may have reinforced their activity avoidance. Interventions for juvenile FM should include a focus on correcting functional deficits and instilling greater confidence in adolescents with juvenile FM to engage in exercise to improve functional outcomes.

Long-term outcomes of adolescents with juvenile-onset fibromyalgia in early adulthood.

OBJECTIVE: This prospective longitudinal study examined the long-term physical and psychosocial outcomes of adolescents with juvenile-onset fibromyalgia (JFM), compared with healthy control subjects, into early adulthood. METHODS: Adolescent patients with JFM initially seen at a pediatric rheumatology clinic (n = 94) and age- and gender-matched healthy control subjects (n = 33) completed online measures of demographic characteristics, pain, physical functioning, mood symptoms, and health care utilization at ∼6 years' follow-up (mean age: 21 years). A standard in-person tender-point examination was conducted. RESULTS: Patients with JFM had significantly higher pain (P < .001), poorer physical function (P < .001), greater anxiety (P < .001) and depressive symptoms (P < .001), and more medical visits (P < .001)than control subjects. The majority (>80%) of JFM patients continued to experience fibromyalgia symptoms into early adulthood, and 51.1% of the JFM sample met American College of Rheumatology criteria for adult fibromyalgia at follow-up. Patients with JFM were more likely than control subjects to be married and less likely to obtain a college education. CONCLUSIONS: Adolescent patients with JFM have a high likelihood of continued fibromyalgia symptoms into young adulthood. Those who met criteria for fibromyalgia in adulthood exhibited the highest levels of physical and emotional impairment. Emerging differences in educational attainment and marital status were also found in the JFM group. JFM is likely to be a long-term condition for many patients, and this study for the first time describes the wide-ranging impact of JFM on a variety of physical and psychosocial outcomes that seem to diverge from their same-age peers.

Dietary intake following experimentally restricted sleep in adolescents.

STUDY OBJECTIVE: To examine the relationship between sleep and dietary intake in adolescents using an experimental sleep restriction protocol. DESIGN: Randomized crossover sleep restriction-extension paradigm. SETTING: Sleep obtained and monitored at home, diet measured during an office visit. PARTICIPANTS: Forty-one typically developing adolescents age 14-16 years. INTERVENTIONS: The 3-week protocol consisting of a baseline week designed to stabilize the circadian rhythm, followed randomly by 5 consecutive nights of sleep restriction (6.5 hours in bed Monday-Friday) versus healthy sleep duration (10 hours in bed), a 2-night washout period, and a 5-night crossover period. MEASUREMENTS: Sleep was monitored via actigraphy and teens completed validated 24-hour diet recall interviews following each experimental condition. RESULTS: Paired-sample t-tests examined differences between conditions for consumption of key macronutrients and choices from dietary categories. Compared with the healthy sleep condition, sleep-restricted adolescents' diets were characterized by higher glycemic index and glycemic load and a trend toward more calories and carbohydrates, with no differences in fat or protein consumption. Exploratory analyses revealed the consumption of significantly more desserts and sweets during sleep restriction than healthy sleep. CONCLUSIONS: Chronic sleep restriction during adolescence appears to cause increased consumption of foods with a high glycemic index, particularly desserts/sweets. The chronic sleep restriction common in adolescence may cause changes in dietary behaviors that increase risk of obesity and associated morbidity.

Quality of life and emotional functioning in youth with chronic migraine and juvenile fibromyalgia.

SUMMARY: Chronic pain in children is associated with significant negative impact on social, emotional, and school functioning. Previous studies on the impact of pain on children's functioning have primarily used mixed samples of pain conditions or single pain conditions (eg, headache and abdominal pain) with relatively small sample sizes. As a result, the similarities and differences in the impact of pain in subgroups of children with chronic pain have not been closely examined. OBJECTIVE: To compare pain characteristics, quality of life, and emotional functioning among youth with pediatric chronic migraine (CM) and juvenile fibromyalgia (JFM). METHODS: We combined data obtained during screening of patients for 2 relatively large intervention studies of youth (age range, 10 to 18 y) with CM (N=153) and JFM (N=151). Measures of pain intensity, quality of life (Pediatric Quality of Life; PedsQL, child and parent-proxy), depressive symptoms (Children's Depression Inventory), and anxiety symptoms (Adolescent Symptom Inventory-4-Anxiety subscale) were completed by youth and their parent. A multivariate analysis of covariance controlling for effects of age and sex was performed to examine differences in quality of life and emotional functioning between the CM and JFM groups. RESULTS: Youth with JFM had significantly higher anxiety and depressive symptoms, and lower quality of life in all domains. Among children with CM, overall functioning was higher but school functioning was a specific area of concern. DISCUSSION: Results indicate important differences in subgroups of pediatric pain patients and point to the need for more intensive multidisciplinary intervention for JFM patients.

Physical activity monitoring in adolescents with juvenile fibromyalgia: findings from a clinical trial of cognitive-behavioral therapy.

OBJECTIVE: Juvenile fibromyalgia (JFM) is a chronic musculoskeletal pain condition that is associated with reduced physical function. Recent research has demonstrated that cognitive-behavioral therapy (CBT) is effective in improving daily functioning among adolescents with JFM. However, it is not known whether these improvements were accompanied by increased physical activity levels. Our objective was to analyze secondary data from a randomized clinical trial of CBT to examine whether CBT was associated with improvement in objectively measured physical activity and whether actigraphy indices corresponded with self-reported functioning among adolescents with JFM. METHODS: Participants were 114 adolescents (ages 11-18 years) recruited from pediatric rheumatology clinics that met criteria for JFM and were enrolled in a clinical trial. Subjects were randomly (1:1) assigned to receive either CBT or fibromyalgia education (FE). Participants wore a hip-mounted accelerometer for 1 week as part of their baseline and posttreatment assessments. RESULTS: The final sample included 68 subjects (94% female, mean age 15.2 years) for whom complete actigraphy data were obtained. Actigraphy measures were not found to correspond with self-reported improvements in functioning. While self-reported functioning improved in the CBT condition compared to FE, no significant changes were seen in either group for activity counts, sedentary, moderate, or vigorous activity. The CBT group had significantly lower peak and light activity at posttreatment. CONCLUSION: Actigraphy monitoring provides a unique source of information about patient outcomes. CBT intervention was not associated with increased physical activity in adolescents with JFM, indicating that combining CBT with interventions to increase physical activity may enhance treatment effects.