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Purpose of Review This review summarizes key findings from recent investigations of psychological interventions for pediatric headache disorders and discusses important avenues for future research. Recent Findings Cognitive Behavioral Therapy (CBT) is effective in reducing headache days among youth with chronic headache. There is mixed evidence for the benefit of CBT on reducing disability associated with migraine, suggesting that there is room to optimize CBT by leveraging complementary or alternative psychological interventions, such as Acceptance and Commitment Therapy (ACT) and mindfulness-based approaches. Tailoring CBT may be especially important for youth with more impairing or complex clinical presentations, such as those with continuous headache. Using eHealth and novel study designs to expand access to and dissemination of psychological interventions is promising. Summary Although CBT is the gold standard psychological treatment for youth with migraine, we are only beginning to understand how and why it is effective. Other promising psychological treatments are available, and studies are beginning to examine how CBT can be optimized to fit the unique needs of each patient. Improving access and equitability of care for youth with migraine will require tailoring psychological treatments for patients with varying headache presentations and youth from a variety of cultural, racial, ethnic, and linguistic backgrounds.

Objective Identify preventive medication treatment response trajectories among youth participating in the Childhood and Adolescent Migraine Prevention study. Methods Data were evaluated from 328 youth (ages 8–17). Childhood and Adolescent Migraine Prevention study participants completed headache diaries during a 28-day baseline period and a 168-day active treatment period during which youth took amitriptyline, topiramate, or placebo. Daily headache occurrence trajectories were established across baseline and active treatment periods using longitudinal hierarchical linear modeling. We tested potential treatment group differences. We also compared final models to trajectory findings from a clinical trial of cognitive behavioral therapy plus amitriptyline for youth with chronic migraine to test for reproducibility. Results Daily headache occurrence showed stability across baseline. Active treatment models revealed decreases in headache frequency that were most notable early in the trial period. Baseline and active treatment models did not differ by treatment group and replicated trajectory cognitive behavioral therapy plus amitriptyline trial findings. Conclusions Replicating headache frequency trajectories across clinical trials provides strong evidence that youth can improve quickly. Given no effect for medication, we need to better understand what drives this clinically meaningful improvement. Results also suggest an expected trajectory of treatment response for use in designing and determining endpoints for future clinical trials. Trial Registration. ClinicalTrials.gov Identifier: NCT01581281

Explore predictors of improvement in headache days and migraine-related disability through a secondary analysis of the cognitive-behavioral therapy plus amitriptyline trial in children and adolescents (Clinical Trials Registration Number: NCT00389038). Participants were 135 youth aged 10–17 years old diagnosed with chronic migraine. Predictor variables included group assignment (treatment or control), baseline scores from depression and quality of life measures, and demographic variables. Criterion variables included headache days and migraine-related disability. Higher baseline depression scores were indicative of more days with headache post-treatment regardless of group assignment. Family income at the higher-end of the low-income range was significantly associated with less migraine-related disability regardless of group assignment (Household Income: HINC-01 in The United States Census Bureau. Bureau, U, 2020). Results from this secondary analysis identify depression symptoms and family income as predictors that can impact headache frequency and migraine-related disability. Self-reported symptoms of depression and family income are important factors to consider as part of the biopsychosocial model of care.

OBJECTIVE: To determine whether a smartphone application (app) with an electronic headache diary and a progressive muscle relaxation (PMR) intervention is feasible and acceptable to people presenting to the Emergency Department (ED) with migraine. METHODS: This single arm prospective study assessed feasibility by actual use of the app and acceptability by satisfaction with the app. We report preliminary data on change in migraine disability and headache days. RESULTS: The 51 participants completed PMR sessions on a mean of 13±19 (0,82) days for the 90-day study period, lasting a median of 11 minutes (IQR 6.5, 17) each. Median number of days of diary use was 34 (IQR 10, 77). Diaries were completed at least twice a week in half of study weeks (337/663). Participants were likely (≥4/5 on a 5-point Likert scale) to recommend both the app (85%) and PMR (91%). MIDAS scores significantly decreased by a mean of 38 points/participant (p

Migraine is a neurological disorder that affects millions of children and adolescents worldwide. Chronic migraine is a subtype of migraine in which patients experience headaches for more days than not each month, with accompanying symptoms of phonophobia, photophobia, nausea or vomiting for most of these headaches. The burden and impact of chronic migraine in the daily lives of children and adolescents is substantial, requiring a holistic, multidisciplinary, and biopsychosocial approach to conceptualization and treatment. The purpose of this review is to provide a comprehensive "2022" overview of acute and preventive treatments for the management of chronic migraine in youth. We first describe diagnostic criteria for chronic migraine and highlight the state of evidence for acute and preventive treatment in children and adolescents. We then discuss emerging treatments currently receiving rigorous clinical research effort, special considerations for the treatment of chronic migraine in children and adolescents, and avenues for improving existing treatments and expanding access to evidence-based care.

OBJECTIVE To compare spatial pain modulation capabilities between adolescents with and without migraine. BACKGROUND Conditioned pain modulation (CPM) responses at the leg are similar in adolescents with versus without migraine. However, the anatomical region of testing may affect spatial pain modulation capabilities as differences in nociceptive processing between patients with migraine and healthy controls are found in local areas that are near the site of clinical pain but not in nonlocal areas. This study aimed to examine spatial pain modulation capabilities tested by the CPM paradigm using test stimulus applied to a local body area. METHODS Nineteen adolescents with migraine (age 14.9 ± 2.3, mean ± SD; 16 female) and 20 healthy adolescents (age 13.8 ± 2.5, mean ± SD; 16 female) completed this case-control study at Cincinnati Children's Hospital Medical Center. Pressure pain thresholds (PPT) were assessed at the trapezius before and during immersion of the foot in a cold water bath (8°C). RESULTS In the migraine group (146.0 ± 79.1, mean ± SD), compared to healthy controls (248.0 ± 145.5, mean ± SD), significantly lower PPT (kilopascal) values were found (estimate = 124.28, 95% CI: 58.98, 189.59, p

Objective Scalable, accessible forms of behavioral therapy for migraine prevention are needed. We assessed the feasibility and acceptability of progressive muscle relaxation (PMR) delivered by a smartphone application (app) in the Primary Care setting. Methods This pilot study was a non-blinded, randomized, parallel-arm controlled trial of adults with migraine and 4+ headache days/month. Eligible participants spoke English and owned a smartphone. All participants were given the RELAXaHEAD app which includes an electronic headache diary. Participants were randomized to receive 1 of the 2 versions of the app-one with PMR and the other without PMR. The primary outcomes were measures of feasibility (adherence to the intervention and diary entries during the 90-day interval) and acceptability (satisfaction levels). We conducted exploratory analyses to determine whether there was a change in Migraine Disability Assessment Scale (MIDAS) scores or a change in headache days. Results Of 139 participants (77 PMR, 62 control), 116 (83%) were female, mean age was 41.7 ± 12.8 years. Most patients 108/139 (78%) had moderate-severe disability. Using a 1-5 Likert scale, participants found the app easy to use (mean 4.2 ± 0.7) and stated that they would be happy to engage in the PMR intervention again (mean 4.3 ± 0.6). For the first 6 weeks, participants practiced PMR 2-4 days/week. Mean per session duration was 11.1 ± 8.3 minutes. Relative to the diary-only group, the PMR group showed a greater non-significant decline in mean MIDAS scores (-8.7 vs -22.7, P = .100) corresponding to a small-moderate mean effect size (Cohen's d = 0.38). Conclusion Smartphone-delivered PMR may be an acceptable, accessible form of therapy for migraine. Mean effects show a small-moderate mean effect size in disability scores.

Objective To describe the headache characteristics and functional disability of a large sample of treatment-seeking youth with continuous headache and compare these factors across diagnostic subgroups of chronic migraine and new daily persistent headache. Methods This retrospective study utilized clinical information (e.g. diagnosis, headache features, medication overuse, functional disability) from a large data repository of patients initially presenting to a multidisciplinary headache center with continuous headache. Patient inclusion in subgroup analyses for chronic migraine and new daily persistent headache was based on clinician diagnosis using International Classification of Headache Disorders (ICHD) criteria. Results The current sample included 1170 youth (mean age = 13.95 years, 78.8% female) with continuous headache. The overwhelming majority of these youth had headaches with migrainous features, regardless of their clinical diagnosis. Youth with chronic migraine reported a longer history of continuous headache symptoms and earlier age of headache onset than youth with new daily persistent headache and were more likely to have medication overuse. Most youth with continuous headache experienced severe migraine-related functional disability, regardless of diagnostic subgroup. Conclusions Overall, youth with continuous chronic migraine and new daily persistent headache did not have clinically meaningful differences in headache features and associated disability. Findings suggest that chronic migraine and new daily persistent headache may be variants of the same underlying disease.

This case-control study examines if measures of subjective and objective (actigraphic) sleep difficulties mediate alterations in amygdalar connectivity in adolescents with migraine compared to healthy adolescents.Adolescents with migraine have different functional connectivity of the amygdala compared to individuals without migraine. Sleep is often disturbed in adolescents with migraine, and could contribute to the alterations in functional connectivity.Twenty adolescents with migraine and 20 healthy controls were recruited from Cincinnati Children's Hospital. Participants completed surveys about their headaches and overall sleep quality, sleep hygiene, and perceived sleep difficulties (Insomnia Severity Scale [ISI]); completed wrist-worn actigraphy; and underwent a magnetic resonance imaging scan.Adolescents with migraine differed from healthy controls only in perceived difficulty in sleep initiation and maintenance (ISI: 8.5 ± 4.7 and 4.5 ± 3.7 [mean ± standard deviation], -4.00 [95% confidence: -6.7 to -1.3], p = 0.005) and had greater functional connectivity between the amygdala and the posterior cingulate cortex, precuneus, dorsolateral prefrontal, sensorimotor, and the occipital cortexes. The differences in functional connectivity of the amygdala were not mediated by the subjective/objective sleep measures (ISI/wake minutes after sleep onset).Adolescents with migraine have greater connectivity between the amygdala and areas involved in sensory, affective, and cognitive aspects of pain. These alterations may not be due to higher levels of sleep difficulties in adolescents with migraine, suggesting that both amygdala and sleep alterations may play an independent role in migraine pathophysiology. This advances the understanding of the mechanisms underlying pediatric migraine and can potentially advance migraine management.

Behavioral headache management is central to a comprehensive care plan for children and adolescents with primary headaches. In fact, The American Academy of Neurology and American Headache Society practice guidelines recommend behavioral headache treatment as a first line preventive intervention for pediatric headache. Behavioral treatment goals are numerous, including: reducing the frequency and severity of headache pain; increasing the patient’s sense of control of their headaches; reducing related disabilities and symptoms; and for some patients, limiting reliance on ineffective, poorly tolerated, and/or unwanted medications.

Key Points Question How do children and adolescents with migraine function after participating in a multicenter migraine prevention medication trial? Findings This survey study that followed up 205 participants from the Childhood and Adolescent Migraine Prevention study at 3, 6, 12, 18, 24, and 36 months found that regardless of treatment group (amitriptyline, topiramate, placebo), youth consistently maintained meaningful reductions of headache days and migraine-related disability for 3 years after completion of the trial. Less than 10% of the participants reported ongoing use of prevention medication prescribed as part of typical clinical care, with most participants reporting no medication use at most time points. Meaning These findings suggest that children and adolescents may get better and sustain positive outcomes over time without ongoing pharmacotherapy., This survey study assesses migraine prevalence and disability of participants who completed the Childhood and Adolescent Migraine Prevention trial during 3 years of follow-up., Importance Migraine is a common neurological disease that often begins in childhood and continues into adulthood; approximately 6 million children and adolescents in the United States cope with migraine, and many frequently experience significant disability and multiple headache days per week. Although pharmacological preventive treatments have been shown to offer some benefit to youth with migraine, additional research is needed to understand whether and how these benefits are sustained. Objective To survey clinical status of youth with migraine who participated in the 24-week Childhood and Adolescent Migraine Prevention (CHAMP) trial over a 3-year follow-up period. Design, Setting, and Participants This survey study used internet-based surveys collected from youth ages 8 to 17 years at 3, 6, 12, 18, 24, and 36 months after completion of the CHAMP trial, which randomized participants to amitriptyline, topiramate, or placebo. At the end of the trial, the study drug was stopped, and participants received clinical care of their choice thereafter. The CHAMP trial was conducted between May 2012 and November 2015, and survey follow-up was conducted June 2013 to June 2018. Participants in this survey study were representative of those randomized in the trial. Data were analyzed from March 2020 to April 2021. Exposures Survey completion. Main Outcomes and Measures Headache days, disability (assessed using the Pediatric Migraine Disability Scale [PedMIDAS]), and self-report of ongoing use of prescription preventive medication. Results A total of 205 youth (mean [SD] age, 14.2 [2.3] years; 139 [68%] girls; mean [SD] history of migraine, 5.7 [3.1] years) participated in the survey. Retention of participants was 189 participants (92%) at month 6, 182 participants (88%) at month 12, 163 participants (80%) at month 18, 165 participants (80%) at month 24, and 155 participants (76%) at month 36. Over the course of the 3-year follow-up, participants consistently maintained meaningful reductions in headache days (mean [SD] headache days per 28 days: CHAMP baseline, 11.1 [6.0] days; CHAMP completion, 5.0 [5.7] days; 3-year follow-up, 6.1 [6.1] days) and disability (mean [SD] score: CHAMP baseline, 40.9 [26.4]; CHAMP completion, 17.9 [22.1]; 3-year follow-up, 12.3 [20.0]). At 3 years after completion of the CHAMP trial, headache days were approximately 1.5 per week (changed from about 3 per week at trial baseline) and disability had improved from the moderate range to the low mild range on the PedMIDAS. Longitudinal analyses showed that amitriptyline and topiramate did not explain intercept random effects for either mean rate of headache days per week (amitriptyline: estimate [SE], 0.07 [0.05]; P = .16; topiramate: estimate [SE], 0.04 [0.05]; P = .50) or headache disability PedMIDAS total score (amitriptyline: estimate [SE], 0.25 [0.38]; P = .52; topiramate: estimate [SE], −0.09 [0.39]; P = .82) changes over time. Of 153 participants who reported on prescription drug use at 3 years, only 1 participant (1%) reported using prevention medication, and most participants reported no medication use at most time points. Conclusions and Relevance These findings suggest that children and adolescents with longer than 5 years history of migraine who participated in the CHAMP trial may sustain positive clinical outcomes over time, even after discontinuing preventive pill-based treatment. This survey study could inform use and discontinuation timing of pharmacological preventive therapies for migraine in youth ages 8 to 17 years. Research is needed to examine mechanisms of treatment improvement and maintenance for preventive therapies, as well as placebo, in the pediatric population.

Objectives We conducted focus groups in people who had participated in mobile health (mHealth) studies of behavioral interventions for migraine to better understand: (a) Participant experience in the recruitment/enrollment process; (b) participant experience during the studies themselves; (c) ideas for improving participant experience for future studies. Methods We conducted four focus groups in people who had agreed to participate in one of three studies involving mHealth and behavioral therapy for migraine. Inclusion criteria were being age 18–80, owning a smartphone, and having four or more headache days per month. All participants met the International Classification of Headache Disorders third edition beta version criteria for migraine. Exclusion criteria were not speaking English and having had behavioral therapy for migraine in the past year. Focus groups were audio recorded, fully transcribed and coded using general thematic analysis. Results The 12 focus group participants had a mean age of 45 ± 15, a mean age of headache onset of 21 ± 13 and mean MIDAS disability score was 39 ± 56. Participants were women (100%), white (50%), Asian (33.3%) or members of other racial groups (16.7%). Certain themes emerged from each topic area. With regard to recruitment/enrollment (a), key themes were: (i) Participants joined their study out of an interest in research and/or a desire to try a new migraine treatment modality (behavioral therapy) . (ii) Enrollment should be simple and study requirements should be carefully explained prior to enrollment. When asked about their experiences during the studies (b), the following themes emerged: (i) It is difficult to participate in study follow-up and compliance phone calls; (ii) participants prefer to choose from among various options for contact with the study team; (iii) there are barriers that limit app use related to migraine itself, as well as other barriers; (iv) completing diaries on a daily basis is challenging; (v) technical difficulties and uncertainties about app features limit use; (vi) being part of a research study promoted daily behavioral therapy use; (vii) progressive muscle relaxation (PMR) is enjoyable, and has a positive impact on life; (viii) behavioral therapy was a preferred treatment to reduce migraine pain. Ideas for improving study design or patient experience (c) included: (i) Increased opportunity to interact with other people with migraine would be beneficial; (ii) navigating the app and data entry should be easier; (iii) more varied methods for viewing the data and measures of adherence are needed; (iv) more information on and more varied behavioral treatment modalities would be preferred. Conclusion Though people with migraine are motivated to participate in mHealth and behavioral treatment studies, better communication up front about interventions as well as greater flexibility in interventions and follow-up methods are desired.

ObjectiveTo provide updated evidence-based recommendations for migraine prevention using pharmacologic treatment with or without cognitive behavioral therapy in the pediatric population.MethodsThe authors systematically reviewed literature from January 2003 to August 2017 and developed practice recommendations using the American Academy of Neurology 2011 process, as amended.ResultsFifteen Class I–III studies on migraine prevention in children and adolescents met inclusion criteria. There is insufficient evidence to determine if children and adolescents receiving divalproex, onabotulinumtoxinA, amitriptyline, nimodipine, or flunarizine are more or less likely than those receiving placebo to have a reduction in headache frequency. Children with migraine receiving propranolol are possibly more likely than those receiving placebo to have an at least 50% reduction in headache frequency. Children and adolescents receiving topiramate and cinnarizine are probably more likely than those receiving placebo to have a decrease in headache frequency. Children with migraine receiving amitriptyline plus cognitive behavioral therapy are more likely than those receiving amitriptyline plus headache education to have a reduction in headache frequency.RecommendationsThe majority of randomized controlled trials studying the efficacy of preventive medications for pediatric migraine fail to demonstrate superiority to placebo. Recommendations for the prevention of migraine in children include counseling on lifestyle and behavioral factors that influence headache frequency and assessment and management of comorbid disorders associated with headache persistence. Clinicians should engage in shared decision-making with patients and caregivers regarding the use of preventive treatments for migraine, including discussion of the limitations in the evidence to support pharmacologic treatments.

OBJECTIVES: To characterize the short-term prognosis of a clinical population of pediatric and young adult patients with migraine and explore predictors of clinical worsening while in care. METHODS: This was a retrospective study of all migraine patients seen at the Cincinnati Children’s Hospital Headache Center from 09/01/2006 to 12/31/2017, who had at least one follow-up visit within 1–3 months of the index visit analyzed. Included data were: age, sex, race, primary ICHD diagnosis, chronic migraine, medication overuse, history of status migrainosus, BMI percentile, headache frequency, headache severity, PedMIDAS score, allodynia, preventive treatment type, lifestyle habits, disease duration, depressive and anxiety symptoms. Clinical worsening was defined as an increase of 4 or more headache days per month between the index visit and the follow-up visit. RESULTS: Data for 13,160 visit pairs (index and follow-up), from 5,316 patients were analyzed. Clinical worsening occurred in only 14.5% (1,908/13,160), whereas a reduction in headache frequency was observed in 56.8% of visit intervals (7,475/13,160), with 34.8% of the intervals (4,580/13,160) showing a reduction of 50% or greater. The change in headache frequency was minimal (increase in 0–3 headaches/month) in 28.7% of intervals (3,737/13,160). In the multivariable model, the odds of worsening were significantly higher with increasing age, female sex, chronic migraine, status migrainosus, depressive symptoms, higher PedMIDAS scores, and use of nutraceuticals, whereas the odds of worsening were lower for summer visits, caffeine drinkers, higher headache frequencies and use of pharmaceuticals. CONCLUSIONS: The majority of pediatric patients who receive multimodal interdisciplinary care for migraine improve over time. Our findings highlight a set of clinical features that may help in identifying specific factors that may contribute to an unfavorable short-term prognosis.

Inhibitory pain modulation has been reported to be deficient in adults across different types of chronic pain, including migraine. To determine whether a similar phenomenon occurs in youth, we performed a quantitative sensory testing investigation in adolescents with migraine (N = 19). These patients were compared to healthy adolescents with (Fam-His; N = 20) or without (Healthy; N = 29) a family history of migraine (eg, first-degree relative with migraine). Subjects were first familiarized with the stimuli and visual analogue rating scales using graded noxious stimuli (0°C, 43-49°C range). These data were used to explore potential pain sensitivity differences between the groups. Pain inhibition was assessed by conditioned pain modulation (CPM), which used both suprathreshold heat pain (heat CPM) and pressure pain thresholds (pressure CPM) as the test stimuli before and during cold-water immersion (8°C). In response to the graded heat stimuli, Fam-His participants reported higher pain intensity ratings compared with patients with migraine, who in turn reported higher pain intensity ratings than the healthy controls (F = 3.6, [df = 2, 459], P = 0.027). For heat and pressure CPM, there was no significant group difference in the magnitude of CPM responses. Thus, adolescents with migraine and healthy adolescents have similar inhibitory pain modulation capability, despite having marked differences in pain sensitivity. Although Fam-His participants are asymptomatic, they demonstrate alterations in pain processing, which may serve as markers for prediction of migraine development.

Objective To better characterize the ways that migraine affects multiple domains of life. Background Further understanding of migraine burden is needed. Methods Adults with migraine randomized to mindfulness-based stress reduction or headache education arms (n = 81) in two separate randomized clinical trials participated in semistructured in-person qualitative interviews conducted after the interventions. Interviews queried participants on migraine impact on life and were audio-recorded, transcribed, and summarized into a framework matrix. A master codebook was created until meaning saturation was reached and magnitude coding established code frequency. Themes and subthemes were identified using a constructivist grounded theory approach. Results Despite most participants being treated with acute and/or prophylactic medications, 90% (73/81) reported migraine had a negative impact on overall life, with 68% (55/81) endorsing specific domains of life impacted and 52% (42/81) describing impact on emotional health. Six main themes of migraine impact emerged: (1) global negative impact on overall life; (2) impact on emotional health; (3) impact on cognitive function; (4) impact on specific domains of life (work/career, family, social); (5) fear and avoidance (pain catastrophizing and anticipatory anxiety); and (6) internalized and externalized stigma. Participants reported how migraine (a) controls life, (b) makes life difficult, and (c) causes disability during attacks, with participants (d) experiencing a lack of control and/or (e) attempting to push through despite migraine. Emotional health was affected through (a) isolation, (b) anxiety, (c) frustration/anger, (d) guilt, (e) mood changes/irritability, and (f) depression/hopelessness. Cognitive function was affected through concentration and communication difficulties. Conclusions Migraine has a global negative impact on overall life, cognitive and emotional health, work, family, and social life. Migraine contributes to isolation, frustration, guilt, fear, avoidance behavior, and stigma. A greater understanding of the deep burden of this chronic neurological disease is needed to effectively target and treat what is most important to those living with migraine.

Explore predictors of improvement in headache days and migraine-related disability through a secondary analysis of the cognitive-behavioral therapy plus amitriptyline trial in children and adolescents (Clinical Trials Registration Number: NCT00389038). Participants were 135 youth aged 10-17 years old diagnosed with chronic migraine. Predictor variables included group assignment (treatment or control), baseline scores from depression and quality of life measures, and demographic variables. Criterion variables included headache days and migraine-related disability. Higher baseline depression scores were indicative of more days with headache post-treatment regardless of group assignment. Family income at the higher-end of the low-income range was significantly associated with less migraine-related disability regardless of group assignment (Household Income: HINC-01 in The United States Census Bureau. Bureau, U, 2020). Results from this secondary analysis identify depression symptoms and family income as predictors that can impact headache frequency and migraine-related disability. Self-reported symptoms of depression and family income are important factors to consider as part of the biopsychosocial model of care.

Adolescents with migraine have different functional connectivity of the amygdala compared to individuals without migraine. Considering that sleep is often disturbed in those adolescents with migrane, this study examined if measures of subjective and objective (actigraphic) sleep difficulties mediate alterations in amygdalar connectivity in adolescents with migraine compared to healthy adolescents. Twenty adolescents with migraine and 20 healthy controls completed surveys about their headaches and overall sleep quality, sleep hygiene and perceived sleep difficulties, wore a wrist-worn actigraphy, and underwent an MRI scan.Adolescents with migraine differed from healthy controls only in perceived sleep difficulties related to sleep initiation and maintenance (pPerspectiveThis article evaluates the role plays by sleep on neural alterations in adolescents with migraine. It indicates that neural alterations due to migraine are not related to alterations in subjective and actigraphic sleep difficulties. This advances the understanding of the mechanisms underlying pediatric migraine and can potentially advance migraine management.

This study was performed to describe the natural history of CF lung disease in young children over an 18 month period to assess the use of CT scanning as an outcome measure for intervention trials.Chest CT scans were obtained at baseline and after 18 months in 42 two- to six-year-old children with CF. CT scans were scored by 2 experienced radiologists for the presence and severity of bronchiectasis, mucous plugging, and air trapping.Mean age at baseline 3.5 (1.3) (mean, sd) years. One or more findings of CF lung disease was seen on the first CT in 27 (64%) and at 18 months in 30 (75%). From baseline to 18 months bronchiectasis, mucous plugging, and air trapping increased from 50% to 53%, 14% to 28%, and 48% to 58% respectively. There was marked variability in the rate of progression, with subjects commonly showing improvement in lung disease. Bronchiectasis worsened in 14 (33%) and improved in 13 (31%). Single subjects with F508del/class III and F508del/class V demonstrated greater worsening and improvement respectively than F508del homozygous and class I genotypes.The natural history of CF lung disease over 18 months varies widely between subjects. Factors including genotype may affect natural history as well as the effectiveness of mediators and could be an important confounder if not recognized. These findings suggest that the use of CT scanning as an outcome surrogate for CF lung disease in young children may be more challenging than has been previously recognized.

Objective There is limited information regarding the potential effect macronutrients have on postprandial glycemic variability in young children with type 1 diabetes (T1D). To date, studies examining nutrition and glycemic outcomes either assess these factors at a single timepoint, or aggregate large datasets for group level analyses. This study examined how inter- and intraindividual fluctuations in carbohydrate, fat, and protein intake impact glycemic variability in the postprandial period for young children with T1D. Methods Thirty-nine young children, aged 2–6 years, wore a continuous glucose monitor for 72 hr, while their parents completed detailed diet records of all food intake. The analyses tested three multilevel models to examine intra- and interindividual differences between food intake and postprandial glycemic variability. Results The results suggest carbohydrate intake, relates to greater postprandial glycemic variability. In contrast, the results reveal the inverse effect for protein, suggesting a tendency for young children who ate more protein at some meals to have lower postprandial glycemic variability, with the exception of lunch. There was no effect for fat on postprandial glycemic variability. Conclusion These results suggest protein consumption may be an important consideration when aiming for optimal glycemic levels for some meals. When counseling parents of young children with T1D on common behaviors underlying glycemic excursion, pediatric psychologists may consider discussing the nutritional make up of children’s meals. Further, the results demonstrate retaining longitudinal data at the person level, versus aggregating individual data for group level analyses, may offer new information regarding macronutrient intake and glycemic outcomes.

OBJECTIVE The objective of this study was to design, code, and pilot test the feasibility and preliminary efficacy of a self-management digital therapeutic tool for adolescents with migraine. BACKGROUND Self-management of migraine in adolescents is complex and has important implications for health outcomes. A comprehensive and accessible approach to self-management is needed for youth with migraine, their parents, and clinicians. METHODS An iterative co-design process was used to develop and optimize the Migraine Manager's digital therapeutic self-management tool. Subsequently, 40 adolescents, age 11-18 years, were enrolled in an 8-week single-arm open label trial (N = 36 analyzed). The primary outcome was headache days. RESULTS Usage data for Migraine Manager were similar to other health app usage data and feedback from participants was uniformly positive, indicating acceptable feasibility. Preliminary efficacy was demonstrated by a reduction in headache days from 17.2 ± 8.5 at baseline to 7.9 ± 7.2 at 8 weeks (95% CI, -13.0 to -7.8; P

The current review presents findings from investigations of migraine in children. The presentation of pediatric migraine, related consequences, and medication treatments are reviewed.A number of advancements have been made in the study of the presentation, disability, and treatments for migraine in children. However, recent research suggests that not all approaches are equally effective in the treatment of migraine in children. Specifically, a recent study comparing pharmacological interventions found that preventive medications were not statistically more effective than placebo in children. Consistent findings showing clinically meaningful placebo response rates, shorter duration of headaches and other characteristic features (e.g. frontal, bilateral location) have been barriers to the design of randomized clinical trials in children and adolescents with migraine. Better understanding of treatment mechanisms for medication interventions is needed.Several migraine treatments have determined to be effective for use in children but few controlled studies have evaluated the effectiveness of medication treatments. Recent research suggests that preventive medications may not be more effective than placebo. Additional research is needed to evaluate the effectiveness of medication treatment in migraine headache care.

Purpose of review To highlight current evidence supporting the prescription of cognitive behavioral therapy (CBT) as part of first-line preventive treatment for children and adolescents with headache and discuss a research strategy aimed at: (1) understanding how and why CBT works, and (2) developing effective and efficient approaches for integrating CBT into headache specialty, neurology, and primary care settings. Recent findings Although preventive medications for pediatric headache and migraine are commonly prescribed, recent meta-analyses and an NIH-funded, multi-center clinical trial suggests that the effect of pill-taking therapies may be mostly due to a placebo effect. These findings have led to greater consideration of prescription of non-pharmacological therapies as first-line interventions (either alone or in combination with pill-based therapy). A literature that extends back to the 1980s and includes recent clinical trials and meta-analyses demonstrates that CBT decreases headache frequency and related disability in youth with headache and migraine and has a favorable benefit to risk profile with almost no negative side effects. Summary CBT has been repeatedly demonstrated as effective in treating pediatric headache and migraine. As such, it should be considered as part of first-line preventive treatment for pediatric headache (either alone or in combination with a pill-based therapy). We need to better understand how this therapy works and what makes it distinct (if anything) from the placebo effect. What we need to achieve is empirical support for efficient access to this evidence-based treatment and clarity on how to match the intensity of non-pharmacological intervention to the needs of our patients at the time they present for care.

OBJECTIVES To characterize a population of pediatric patients visiting an infusion center for acute migraine and determine predictors of first-line treatment success in this population. BACKGROUND Though migraine is common in the pediatric emergency department and specialized infusion centers, little is known about this patient population and whether or not clinical data can be used to predict treatment response. METHODS This was an observational study involving a retrospective analysis of data from visits to the Cincinnati Children's Hospital infusion center for treatment of an acute migraine. Data were extracted from a database and chart reviews were completed for missing or outlying data. Descriptive statistics were used to outline patient: sex, age, race, primary ICHD-III diagnosis, chronic migraine, medication overuse headache (MOH), headache frequency, month of treatment, headache severity, headache duration, use of acute medication at home in the past 24 hours and treatment received (metoclopramide vs prochlorperazine and dexamethasone vs no dexamethasone). The odds of success of first-line intervention were modeled using simple logistic regression with the above characteristics used as predictors. Predictors with a P value

Objective To evaluate the frequency with which migraine patients initiated behavioral migraine treatment following a headache specialist recommendation and the predictors for initiating behavioral migraine treatment. Methods We conducted a prospective cohort study of consecutive patients diagnosed with migraine to examine whether the patients initiated behavioral migraine treatment following a provider recommendation. The primary outcome was scheduling the initial visit for behavioral migraine treatment. Patients who initiated behavioral migraine treatment were compared with those who did not (demographics, migraine characteristics, and locus of control) with analysis of variance and chi-square tests. Results Of the 234 eligible patients, 69 (29.5%) were referred for behavioral treatment. Fifty-three (76.8%) patients referred for behavioral treatment were reached by phone. The mean duration from time of referral to follow-up was 76 (median 76, SD = 45) days. Thirty (56.6%) patients initiated behavioral migraine treatment. There was no difference in initiation of behavioral migraine treatment with regard to sex, age, age of diagnosis, years suffered with headaches, health care utilization visits, Migraine Disability Assessment Screen, and locus of control (P > 0.05). Patients who had previously seen a psychologist for migraine were more likely to initiate behavioral migraine treatment than patients who had not. Time constraints were the most common barrier cited for not initiating behavioral migraine treatment. Conclusions Less than one-third of eligible patients were referred for behavioral treatment, and only about half initiated behavioral migraine treatment. Future research should further assess patients' decisions regarding behavioral treatment initiation and methods for behavioral treatment delivery to overcome barriers to initiating behavioral migraine treatment.

OBJECTIVE: The goal of this study was to determine which cognitive behavioral therapy (CBT-HA) treatment components pediatric headache patient stakeholders would report to be most helpful and essential to reducing headache frequency and related disability in order to develop a streamlined, less burdensome treatment package that would be more accessible to patients and families. BACKGROUND: Pediatric migraine is a prevalent and disabling condition. CBT-HA has been shown to reduce headache frequency and related disability, but may not be readily available or accepted by many migraine sufferers due to treatment burden entailed. Research is needed to determine systematic ways of reducing barriers to CBT-HA. METHODS: Qualitative interviews were conducted with 10 patients and 9 of their parents who had undergone CBT-HA. Interviews were analyzed using an inductive thematic analysis approach based upon modified grounded theory. Patients were 13 to 17.5 years of age (M = 15.4, SD = 1.63) and had undergone CBT-HA approximately one to two years prior to participating in the study. RESULTS: Overall, patients and their parents reported that CBT-HA was helpful in reducing headache frequency and related disability. Although patients provided mixed reports on the effectiveness of different CBT-HA skills, the majority of patients indicated that the mind and body relaxation skills of CBT-HA (deep breathing, progressive muscle relaxation, and activity pacing in particular) were the most helpful and most frequently used skills. Patients and parents also generally reported that treatment was easy to learn, and noted at least some aspect of treatment was enjoyable. CONCLUSIONS: Results from these qualitative interviews indicate that mind and body CBT-HA relaxation skills emerged as popular and effective based on patient and parent report. Future research examining the effectiveness of streamlined pediatric migraine non-pharmacological interventions should include these patient-preferred skills.

OBJECTIVE To assess the impact of parental migraine on adolescents (aged 13-21 years) living within the parental home from the adolescent's perspective. BACKGROUND Family members are affected by their parent's migraine. We surveyed adolescents on the social, academic, and emotional effects of their parent's migraine. METHODS The Chronic Migraine Epidemiology and Outcomes (CaMEO) study was a longitudinal Web-based study with cross-sectional modules designed to assess migraine symptoms, severity, frequency, and disability; migraine-related consulting practices, healthcare utilization, medication use, comorbid health conditions, and family related burden associated with migraine. The Family Burden Module (adolescent version; FBM-A) from the CaMEO study assessed parents with migraine and adolescent household members (dyads). Adolescents ranged in age from 13-21 years and were living at home with their parent. The initial FBM-A survey included 52 items covering five domains, which was refined and reduced by confirmatory factor analysis to 36 items covering four domains. Depression (9-item Patient Health Questionnaire) and anxiety (7-item Generalized Anxiety Disorder scale) were assessed. Item responses were stratified by parent migraine status (episodic migraine [EM]

Adequate nutrition is essential for growth in children with cystic fibrosis (CF). The new CF Foundation Clinical Practice Guidelines bring attention to monitoring macronutrient intake as well as total energy.Dietary intake of 75 preschool children with CF and pancreatic insufficiency was examined and compared to the Clinical Practice Guidelines. Regression analyses examined relationships between macronutrient intake and growth.Approximately 45% of children met the 110% minimum recommended dietary allowance (RDA) recommendation. Children consumed 35.3% (6.1) of total daily energy intake from fat, 12.7% (1.7) from protein, and 52.0% (6.1) from carbohydrates. Percent energy from protein was associated with height growth.Many preschoolers with CF are not meeting nutrition benchmarks for total energy and fat. To optimize nutrition early, dietary monitoring with frequent individualized feedback is needed. Optimizing intake of macronutrients that promote growth, especially fat and protein, should be a primary clinical target.

We compared headache frequency trajectories between clinical trial participants who received cognitive-behavioral therapy (CBT) and amitriptyline (CBT+A) or headache education (HE) and amitriptyline (HE+A) to determine if there was a differential time course of treatment response between the groups. One hundred thirty-five patients (age 10–17 years) diagnosed with chronic migraine participated, attending 8 one-hour one-on-one CBT or HE sessions with a trained psychologist for 8 weekly sessions, 2 sessions at weeks 12 and 16, and a post-treatment visit at week 20. Participants kept daily headache diaries and completed take-home assignments between visits. Data from daily headache diaries are presented for each day and according to 28-day periods. Trajectories of improvement indicate initial decrease in headache days began during the first month of treatment, for both groups, and continued to decrease throughout treatment. The CBT+A group had greater daily improvement than the HE+A group. A significantly greater proportion of the CBT+A group had a ≥50% reduction in headache days each month, and a significantly greater proportion of the CBT+A group had ≤4 headache days per month in months 3 through 5. Results indicate the trajectory of decrease in headache days is significantly better for patients receiving CBT+A versus HE+A. Perspective This article presents daily information about headache frequency over a 20-week clinical trial. Youth with chronic migraine who received CBT+A improved faster than those in the control group. Findings provide clinicians with evidence-based expectations for treatment response over time and ways of monitoring treatment success. Trial registration clinicaltrials.gov identifier NCT00389038 .

Background: We update the psychometric properties of the Hypoglycemia Fear Survey-Parents of Young Children (HFS-PYC), a 26-item measure of parents' hypoglycemia fear for young children using an insulin pump. Methods: We combined three similar datasets for the analyses. The data analyzed included parents' responses to the HFS-PYC and a demographic form. For a subset of children (n = 91), we also analyzed self-monitoring of blood glucose data. We used confirmatory factor analysis (CFA) to confirm the measure's original factor structure. Additional analyses examined reliability and validity of a revised HFS-PYC for parents of young children using pumps. Results: We analyzed data from 116 parents (93% mothers). Mean child age and HbA1c were 5.2 ± 1.3 years and 8.2% ± 1.1%, respectively. CFA identified a 22-item two-factor solution (χ2 (208, n = 116) = 368.688, P

OBJECTIVE: Correlational studies have linked shortened sleep to adolescents’ report of post-concussion symptoms and cognitive performance during concussion assessments. This study tested whether those are cause-effect relationships. DESIGN: 3-week randomly-counterbalanced, within-subjects, crossover experiment SETTING: Adolescents slept at home with weekly visits to an outpatient clinic for sleep monitor uploads and outcome assessments. PARTICIPANTS: 24 healthy 14–17.9-year-olds CONDITIONS: After an initial sleep-stabilization period, adolescents experienced 5-night spans of Short Sleep (SS; 6.5 hours/night in bed) versus Healthy Sleep Opportunity (HS; 9.5 hours/night in bed). MAIN OUTCOME MEASURES: Cognitive indexes and Post-Concussion Symptom Severity (PCSS) from the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). RESULTS: Adolescents reported significantly worse symptoms on the PCSS after SS than HS, even after excluding items manifestly related to sleep. Verbal Memory was also worse after SS than HS, though the effect was small. The manipulation did not significantly affect other cognitive indexes. CONCLUSIONS: A realistic “dose” of short sleep, similar to what many adolescents experience regularly on school nights, can cause or contribute to symptom reports during concussion assessments. Consistent with prior sleep research, one-on-one cognitive tests appear to be less sensitive than measures of emotional and behavioral functioning to the effects of short sleep.

Cognitive behavioral therapy (CBT) is a psychological intervention that involves development of coping strategies to reduce the experience of pain. Although CBT is a promising intervention to reduce headache days in patients with migraine, it may not be effective for all patients. Thus, there is a need to identify markers that could predict which patients will respond to CBT. We aimed to determine whether baseline brain function and amygdalar connectivity, assessed by functional magnetic resonance imaging, or pain modulation capacities, assessed by the conditioned pain modulation (CPM) response, can predict a reduction in headache days after CBT in adolescents with migraine. Patients with migraine (n = 20; age range 10-17 years) completed 8 weekly CBT sessions. The CPM response was examined in the trapezius and the leg. Headache days significantly decreased after CBT (P < 0.001). Greater functional connectivity before CBT between the right amygdala and frontal gyrus, anterior cingulate cortex, and precentral gyrus was related to greater headache reduction after CBT. Greater reduction in headache days after CBT was related with less efficient CPM response before CBT at the trapezius (r = -0.492, P = 0.028) but not at the leg. This study found that headache reduction after CBT was related to right amygdala connectivity with frontal and sensorimotor regions at baseline as well as baseline pain modulation capacities. These findings suggest that individual differences in brain function and pain modulation can be associated with clinical improvements and help with determination of CBT responsiveness.

OBJECTIVES This basic mechanistic study examined the changes in brain activation and resting-state connectivity after 8 weeks of CBT in youth with migraine. BACKGROUND Cognitive behavioral therapy (CBT) is a psychological intervention that is effective in reducing pain in migraine patients. However, the neural mechanisms underlying CBT in adolescents with migraine are not yet known. METHODS Eighteen adolescents with migraine (15 females, age 15.1 ± 2.1 years [mean ± SD]) completed 8 weekly CBT sessions. Before the first and after the final CBT session, participants underwent structural and resting-state blood-oxygen-level-dependent contrast MRI scans. Arterial spin labeling was also used to examine brain activation during the resting state. For connectivity analyses, the right and left amygdala were chosen as seed regions. Relationships of the time courses within these seeds with voxels across the whole brain were evaluated. RESULTS Headache frequency decreased from 15 ± 7.4 headaches per month before CBT to 10 ± 7.4 after CBT (P

To characterize the clinical features of a large sample of children, adolescents, and young adults with a history of status migrainosus (SM) and to describe their short-term prognosis.Data on the clinical characteristics of children and adolescents with SM are sparse and little is known about the prognosis of this population.This was a retrospective clinical cohort study that included patients from the Cincinnati Children's Headache Center if they had a diagnosis of migraine and data available for a 1-3 months follow-up interval. Data extracted from the initial interval visit (visit A) included: age, sex, race, migraine diagnosis, SM history, chronic migraine, medication overuse headache (MOH), body mass index (BMI), headache frequency, headache severity, disability, allodynia and lifestyle habits: caffeine intake, meal skipping, sleep duration, exercise frequency, and fluid intake. Data extracted from the initial consultation visit included: months with headache at initial consultation visit, patient endorsing "feeling depressed" and anxiety symptoms. Headache frequency and visit type were also measured at the second visit (visit B) in the follow-up interval. A multivariate logistic regression model with a backward elimination procedure was created to model the odds of having a diagnosis of SM using the cross-sectional predictor variables above. Second, chi-square tests were used to compare the proportion of patients with SM to the proportion of patients without SM who had each of the following outcomes in the short-term follow-up window: treatment response (50% or greater reduction in headache frequency), overall reduction in headache frequency (reduction of 1 or more headache days/month), minimal change in headache frequency (increase in 0-3 headache days/month), and clinical worsening (increase in 4 or more headache days/month).A total of 5316 youth with migraine were included and 559 (10.5%) had a history of SM. In the multivariate logistic regression model, predictors significantly associated with SM were: older age (OR = 1.13, 95% CI = 1.09-1.17, P .0001), migraine with aura (MWA) (OR = 1.30, 95% CI = 1.03-1.65, P = .03), MOH (OR = 1.72, 95% CI = 1.30-2.28, P = .0001), headache frequency (OR = 0.99, 95% CI = 0.97-0.99, P = .030), higher headache severity (OR = 1.08, 95% CI = 1.02-1.15, P = .009), months with headache at initial consultation (OR = 1.00, 95% CI = 1.00-1.01, P = .042), and admission to infusion center at visit B (OR = 2.27, 95% CI = 1.38-3.72, P = .001). Patients with a history of SM were more likely to experience an increase in 4 or more headache days per month at follow-up: 15.2% as compared to 11.1% of those without SM, χYouth with SM represent a distinct subgroup of the migraine population and have an unfavorable short-term prognosis.

Objective To present data on psychometric properties of the Psychosocial Assessment Tool 2.0_General (PAT), a brief screener for psychosocial risk in families of youth with medical conditions, in youth with headache. Background Emotional and behavioral disturbances, parent distress, and poor family functioning are common among youth with recurrent migraine and tension-type headache; however, tools to comprehensively screen family and psychosocial risk in youth with headache are not currently available. The PAT could address an important gap by facilitating identification of psychosocial treatment needs among youth with headache. Design and methods Youth with recurrent migraine (with and without aura; chronic migraine) or tension-type headache (episodic and chronic) completed the PAT and validated measures of adolescent emotional and behavioral functioning, parent emotional functioning, and family functioning at baseline (n = 239; 157 from neurology clinic, 82 from the community) and 6-month follow-up (n = 221; 146 from neurology clinic, 75 from the community). Results Internal consistency for the PAT Total score was strong (α = .88). At baseline, the PAT Total score was significantly associated in the expected direction with established measures of child emotional and behavioral functioning (r = .62), parent anxiety and depressive symptoms (r = .49; r = .53, respectively), and family functioning (r = .21). Predictive validity was demonstrated by a significant association between PAT Total scores at baseline with child emotional and behavioral functioning (r = .64), parent anxiety (r = .37), parent depression (r = .42), and family functioning (r = .26) at 6-month follow-up. Conclusions The PAT is a promising tool for screening psychosocial risk that could facilitate identification of psychosocial treatment needs among youth with recurrent headache at risk for poor outcomes.

Progressive muscle relaxation (PMR) is an under-utilized Level A evidence-based treatment for migraine prevention. We studied the feasibility and acceptability of smartphone application (app)-based PMR for migraine in a neurology setting, explored whether app-based PMR might reduce headache (HA) days, and examined potential predictors of app and/or PMR use. In this single-arm pilot study, adults with ICHD3 migraine, 4+ HA days/month, a smartphone, and no prior behavioral migraine therapy in the past year were asked to complete a daily HA diary and do PMR for 20 min/day for 90 days. Outcomes were: adherence to PMR (no. and duration of audio plays) and frequency of diary use. Predictors in the models were baseline demographics, HA-specific variables, baseline PROMIS (patient-reported outcomes measurement information system) depression and anxiety scores, presence of overlapping pain conditions studied and app satisfaction scores at time of enrollment. Fifty-one patients enrolled (94% female). Mean age was 39 ± 13 years. The majority (63%) had severe migraine disability at baseline (MIDAS). PMR was played 22 ± 21 days on average. Mean/session duration was 11 ± 7 min. About half (47%) of uses were 1+ time/week and 35% of uses were 2+ times/week. There was a decline in use/week. On average, high users (PMR 2+ days/week in the first month) had 4 fewer days of reported HAs in month 2 vs. month 1, whereas low PMR users (PMR