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Robert C Gibler,1 Kaelynn E Knestrick,1 Brooke L Reidy,1,2 Daniel N Lax,3,4 Scott W Powers1,2,4 1Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; 2Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; 3Division of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; 4Headache Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USACorrespondence: Robert C Gibler, Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA, Email Robert.Gibler@cchmc.orgAbstract: 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.Keywords: chronic migraine, migraine, headache, children, adolescents, pediatrics

Objective: Previous research demonstrated high rates of perceived mealtime behavior problems in families of young children with type 1 diabetes who were managed with conventional therapy. Because of new insulin regimens that offer greater flexibility, reexamination of mealtime behaviors is required. We assessed parent-reported mealtime behaviors in a sample of young children using an insulin pump. An additional aim was to evaluate the associations of two measures of parental feeding behavior with children's glycemic control. Methods: Primary caregivers of 31 young children (mean age = 5.0 ± 1.3 yr) completed the Child Feeding Questionnaire (CFQ) and the Behavioral Pediatric Feeding Assessment Scale (BPFAS). Hemoglobin A1c (HbA1c) was used as a surrogate marker for children's glycemic control. Results: Children had a mean HbA1c of 7.8 ± 0.64%. Mean CFQ - Restriction and Pressure to Eat scores were 3.1 ± 0.94 and 2.0 ± 0.88, respectively (range = 1-5). Mean BPFAS - Parent and Child scores were 16.0 ± 4.3 (range = 10-50) and 44.9 ± 9.3 (range = 25-125), respectively. Positive correlations were found between children's HbA1c levels and caregivers' reporting of frequency of child mealtime behavior problems. Conclusions: Caregivers of young children on pump therapy report relatively low rates of mealtime behavior problems. However, correlations with children's HbA1c suggest that parent-child mealtime behaviors continue to relate to children's health outcomes. Research is needed to determine if changing mealtime interactions can improve children's glycemic control; items from the BPFAS and CFQ can offer targets to guide interventions. [ABSTRACT FROM AUTHOR]

We describe a new measure of dietary intake in cystic fibrosis (CF): the CF Individualized NuTritional Assessment of Kids Eating (CF INTAKE). Ninety-one children (49 boys, M = 4.5 +/- 3.2 years) participated. Four scores measured Missed Opportunities to maximize calorie intake: Meal, Enzyme, Calorie, and Food Choice Scores. Power Scores measured high-fat food/addables intake. Recommended meals were omitted 10% and enzymes were omitted 15% of the time. More than half of all foods consumed were low-fat foods. Calorie intake was maximized in only one third of foods eaten. The CF INTAKE can identify specific areas to target through individualized nutritional counseling. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To compare the food group variety and nutritional adequacy of the diet between toddlers with cystic fibrosis (CF) and age-matched controls. Subjects A clinical sample of 22 toddlers with CF (mean age=21.3 +/- 7.2 months) matched to a community sample of 22 healthy peers. MAIN OUTCOME MEASURES: The variety index for toddlers (VIT) and the mean adequacy ratio (MAR). RESULTS: Fruit group scores were highest for children with CF (0.95 +/- 0.13; possible range 0.00-1.00), and dairy group scores were highest for controls (0.90 +/- 0.18). All children earned the lowest scores for vegetables (CF: 0.15 +/- 0.12; controls: 0.26 +/- 0.22). No significant differences were found when comparing VIT and MAR scores by sample (P >0.05). A moderate positive relationship was found between total VIT scores and MAR scores for all children (r=0.38, P <0.05). Toddlers with CF did not achieve the 120-150% of Recommended Dietary Allowance (RDA) for energy. CONCLUSIONS: Toddlers with CF are consuming diets that are varied and nutritionally adequate for a healthy child. To optimize nutritional status and growth, current recommendations for toddlers with CF to eat a well-balanced diet and to exceed daily RDA for energy requirements remain key dietary issues. [ABSTRACT FROM AUTHOR]

Objectives: Parents of pre-schoolers with type 1 diabetes report more behavioral feeding problems and concerns about the management of mealtime behavior than parents of age-matched healthy control children. We compared mealtime interactions of 26 families of pre-schoolers with type 1 diabetes (13 boys; mean age = 4.4 yr) and those of 26 families of age-matched control children by using direct observation of meals. Methods: Families had three meals videotaped in their home. Trained coders independently scored each meal for parent, child, and child eating behaviors by using the Dyadic Interaction Nomenclature for Eating (DINE). Results: The frequency of parent and child behaviors at mealtimes (such as instructions to eat, coaxing, feeding, refusing food, leaving the table, and non-compliance with instructions to eat) was similar for both groups. Children ate less and engaged in more behaviors incompatible with eating during the second half of meals than during the first half. Children, who took over 19 min to eat at meals (average duration for controls) played more and ate less than children, who ate more quickly. Conclusions: Despite increased parental concern, pre-schoolers with type 1 diabetes do not have more challenging mealtime behaviors than age-matched healthy controls. Interventions to inform parents of pre-schoolers with type 1 diabetes about typical child mealtime behaviors and teach effective strategies for managing problematic behaviors are needed to reduce parental concerns and may be critical for improving adherence to diet if a relation between child behavior, adherence, and metabolic control is demonstrated. Further research is required to investigate whether these mealtime interactions adversely impact dietary adherence and blood glucose excursion. [ABSTRACT FROM AUTHOR]

This pilot study examined a behavioral treatment to increase calorie intake in toddlers with cystic fibrosis. Eight toddlers were randomly assigned to behavioral plus nutrition (BEH) or nutrition intervention (NTR) conditions. Calorie intake and weight were measured at pre- and posttreatment. The BEH group showed a trend for changes in calorie intake pre- to posttreatment (p = .07; 40% increase). Results for the BEH and NTR groups did not differ significantly. Most participants achieved weight gains consistent with normal growth. Seventy-five percent had not shown this pattern during the year prior to intervention. These results support the feasibility and potential for behavioral interventions in this age group. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Despite the high prevalence of headaches in youths, quality of life (QOL) has not been well examined. We examined QOL in a clinical sample of children with headaches and compared it with children with other chronic diseases. METHODS: A survey study was conducted of 572 consecutive patients (mean age, 11.4 +/- 3.6 years) who presented with headaches to a children's headache center. Children and parents completed the Pediatric Quality of Life Inventory, Version 4.0 and a standardized headache assessment. Results were compared with established norms for healthy and chronically ill children. RESULTS: Most patients (99%) had a clinical diagnosis of migraine: 85% met the International Headache Society migraine criteria, and 40% had chronic daily headaches. Total Pediatric Quality of Life Inventory, Version 4.0 score was lower for the entire group (73.1 +/- 14.4) compared with healthy norms (83.0 +/- 14.8) and lowest for children with chronic daily headaches (70.5 +/- 15.5). The impact on QOL of children with migraine was similar to that of children with arthritis and cancer. CONCLUSIONS: QOL of children with headaches is significantly affected by their health condition. The impact of headaches on QOL is similar to that found for other chronic illness conditions, with impairments in school and emotional functioning being the most prominent. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Infants and toddlers with cystic fibrosis (CF) are at risk for poor growth. Controlled behavioral assessment studies have not focused on this population. This study compared calorie intake, percentage of Recommended Daily Allowance (RDA) per day and per kilogram, and percentage of calories from fat, protein, and carbohydrates between infants and toddlers with CF and healthy peers. Also, eating behaviors, such as meal duration, bites and sips per minute, percentage of meal spent eating, children's problematic eating behaviors, and parents' perceptions of mealtime behaviors were compared between infants and toddlers with CF and controls. Five hypotheses were tested. 1) Infants and toddlers with CF would be comparable to controls on the number of calories consumed per day and the percentage of calories from fat. 2) Infants and toddlers with CF would not meet the CF dietary guidelines for the percentage of RDA for calories or the percentage of calories from fat. 3) Infants and toddlers with CF would have longer meal durations than healthy peers, but would not differ on the pace of eating, the number of calories consumed during the meal, or the percentage of time spent eating during the meal. 4) Parents of infants and toddlers with CF would perceive more problematic mealtime behavior than controls. 5) Parents' perceptions of children's mealtime behavior would positively correlate with meal duration and negatively correlate with the number of calories consumed during the meal. DESIGN: A 2-group comparison study. SETTING/SAMPLE: A clinical sample of 35 infants and toddlers with CF (M = 18.6; standard deviation = 8.1 months; range = 7-35 months) and a community sample of 34 healthy peers matched for age, gender, socioeconomic status, and number of parents and siblings present during mealtimes. MEASUREMENT AND MAIN RESULTS: Children's calorie intake was measured using 3-day diet diaries. The 2 groups did not differ on the total number of calories consumed per day, the percentage of calories derived from fat, or the percentage of RDA consumed per day. Infants and toddlers with CF were not meeting the CF dietary recommendations of 120% to 150% RDA for energy with 40% of calories coming from fat. Using the Dyadic Interaction Nomenclature for Eating, a behavioral coding system, videotaped recordings of children's dinner meals were scored for meal duration, number of bites and sips per minute, number of calories per bite or sip, and the percentage of 10-second intervals with bites and sips. The CF sample had significantly longer mealtimes (20.2 minutes) than the control group (16.4 minutes), but did not differ on calories consumed at the meal, bites and sips per minute, calories per bite and sip, or time spent eating during the meal. On the Behavioral Pediatrics Feeding Assessment Scale, a measure of parental perceptions of mealtime behavior that was completed by a subset of families (39 families), parents of infants and toddlers with CF endorsed a greater number of mealtime behaviors as problems and a higher occurrence of problems than did parents of controls. Examples of these behaviors for the CF sample included problems with their child's willingness to try new foods (48%), eat vegetables (48%), and observations that their child has a poor appetite (32%) and would rather drink than eat (32%). Parents of children with CF chose a greater number of mealtime strategies and feelings as problems and reported more frequently using problematic strategies at mealtimes than did parents of controls. Examples of problematic strategies and feelings for parents of infants and toddlers with CF included feeling anxious/frustrated when feeding their children (37%), not feeling confident that their child eats enough (32%), and using coaxing to get their child to take a bite (26%). For the entire sample, a positive correlation of 0.29 was found between the number of mealtime behavior problems reported by parents and meal duration, suggesting the co-occurrence of problematic mealtime behavior with longer meal duration. No relationship was found between the number of child mealtime behavior problems reported by parents and the number of calories consumed during the filmed meal. For the CF sample, a correlation of -0.26 between children's weight percentile for age and the filmed meal duration was found, suggesting a tendency for meal duration to increase as children's weight for age decreases. Post-hoc analyses were conducted comparing infants and toddlers with previously reported samples of preschool and school-aged children on meal duration. Results demonstrated that in each group, children with CF had longer meals than age-matched controls. CONCLUSIONS: Our findings reveal significant deficits in achieving dietary recommendations for many families of infants and toddlers with CF. Only 11% of infants and toddlers with CF met the CF dietary recommendation of at least 120% of the RDA/day for energy. In addition, infants and toddlers were found to derive only 34% of their daily calories from fat, compared with the recommended 40% needed for a moderate to high fat diet. These results underscore the need for intervention in families of infants and toddlers with CF, who in addition to being at increased risk for malnutrition, may also experience a hastening in the decline of their pulmonary status because of poor nutritional status. Currently, there is limited programmatic research on nutritional and feeding interventions for toddlers and infants with CF. One study, which used a hospital-based behavioral education program to increase the caloric intake of 3 children (ages 10-20 months) who were below the fifth percentile for weight for length, found at least a 54% increase in calories for each child after treatment. Similarly, preliminary findings of 2 parent-based interventions, a nutrition education curriculum and a nutrition education plus behavior parent-training curriculum, found a 22% and 32% increase in daily calories, respectively, at treatment completion. A large-scale clinical trial is needed to evaluate the efficacy of any nutritional intervention before widespread dissemination. Additional assessment-focused research is also needed to identify patients' who may be at greatest risk for malnutrition and to guide the development of interventions to treat them. [Abstract for this article also available on page 947 of printed version. Full article available at www.pediatrics.org] [ABSTRACT FROM AUTHOR]

Determines whether interventions for managing pain in children and adolescents meet the Chambless criteria for well-established treatments. Overview of the Chambless criteria; Effectiveness of cognitive behavioral therapy for procedure-related pain; Recommendations for biobehavioral research.

Background: Chronic daily headache (CDH) and chronic migraine (CM) are one of the most frequent problems encountered in neurology, are often difficult to treat, and frequently complicated by medication-overuse headache (MOH). Proper recognition of MOH may alter treatment outcome and prevent long term disability.Objective: This study identifies the unique genomic expression pattern MOH that respond to cessation of the overused medication.Methods: Baseline occurrence of MOH and typical pattern of response to medication cessation were measured from a large database. Whole blood samples from patients with CM with or without MOH were obtained and their genomic profile was assessed. Affymetrix human U133 plus2 arrays were used to examine the genomic expression patterns prior to treatment and 6-12 weeks later. Headache characterisation and response to treatment based on headache frequency and disability were compared.Results: Of 1311 patients reporting daily or continuous headaches, 513 (39.1%) reported overusing analgesic medication. At follow-up, 44.5% had a 50% or greater reduction in headache frequency, while 41.6% had no change. Blood genomic expression patterns were obtained on 33 patients with 19 (57.6%) overusing analgesic medication with a unique genomic expression pattern in MOH that responded to cessation of analgesics. Gene ontology of these samples indicated a significant number were involved with brain and immunological tissues, including multiple signalling pathways and apoptosis.Conclusions: Blood genomic patterns can accurately identify MOH patients that respond to medication cessation. These results suggest that MOH involves a unique molecular biology pathway that can be identified with a specific biomarker. [ABSTRACT FROM AUTHOR]

Objective: To identify and disseminate research priorities for the headache field that should be areas of research focus during the next 10 years., Background: Establishing research priorities helps focus and synergize the work of headache investigators, allowing them to reach the most important research goals more efficiently and completely., Methods: The Headache Research Priorities organizing and executive committees and working group chairs led a multistakeholder and international group of experts to develop headache research priorities. The research priorities were developed and reviewed by clinicians, scientists, people with headache, representatives from headache organizations, health-care industry representatives, and the public. Priorities were revised and finalized after receiving feedback from members of the research priorities working groups and after a public comment period., Results: Twenty-five research priorities across eight categories were identified: human models, animal models, pathophysiology, diagnosis and management, treatment, inequities and disparities, research workforce development, and quality of life. The priorities address research models and methods, development and optimization of outcome measures and endpoints, pain and non-pain symptoms of primary and secondary headaches, investigations into mechanisms underlying headache attacks and chronification of headache disorders, treatment optimization, research workforce recruitment, development, expansion, and support, and inequities and disparities in the headache field. The priorities are focused enough that they help to guide headache research and broad enough that they are widely applicable to multiple headache types and various research methods., Conclusions: These research priorities serve as guidance for headache investigators when planning their research studies and as benchmarks by which the headache field can measure its progress over time. These priorities will need updating as research goals are met and new priorities arise., (© 2024 American Headache Society.)

Background and Objectives: This cross-sectional observational study retrospectively examined clinical data collected from adolescents and young adults (AYAs) seeking care in a specialty headache clinic. We characterized participants' headache characteristics and psychological functioning and examined the association between self-reported anxiety and depressive symptoms and headache frequency, severity, and disability., Methods: During their clinic visit, AYAs ( M age = 18.36; range = 14-32, 79.5% female) completed an intake questionnaire and reported about their headache characteristics (i.e., frequency, severity, and duration of symptoms in months), mental health history (i.e., previous diagnosis of an anxiety or depressive disorder), and utilization of emergency department (ED) services for migraine. AYAs also completed psychometrically validated screening tools for anxiety and depressive symptoms (i.e., the GAD-7 and PHQ-9). We computed descriptive statistics and examined associations among scores on psychological measures and headache characteristics, including migraine-related disability. We also tested whether individuals with clinically elevated GAD-7 and PHQ-9 scores had higher levels of disability relative to those with fewer/subclinical levels of anxiety and depressive symptoms., Results: Participants ( N = 283) reported more than 19 headache days per month on average, with more than 90% describing their average headache intensity as moderate or severe . Nearly half of AYAs reported severe headache-related disability. Approximately one-quarter of AYAs reported a previous diagnosis anxiety or depressive disorder diagnosis, and more than one-third scored above clinical cutoffs on the PHQ-9 and GAD-7. Higher scores on both psychological screening instruments were associated with greater headache frequency. More than 10% of patients endorsed current suicidal ideation; this was not related to headache-related disability. Participants reported a high degree of ED utilization for headache; these rates were unrelated to endorsement of psychological comorbidities., Discussion: In this sample of AYAs, headache characteristics were generally unrelated to scores on measures on psychological functioning. However, the observed rates of clinically elevated anxiety/depressive symptoms and suicidality in this sample of AYAs underscore the importance of screening for psychological comorbidities in neurology clinics that serve this age group, irrespective of self-reported disability. Results also emphasize the need to expand access to behavioral health services for AYAs with headache disorders and the importance of incorporating a biopsychosocial perspective to the transition of health care from pediatrics to adult neurology practice., Competing Interests: R.C. Gibler and M.A. Marzouk report support from a training grant through the National Institute for Diabetes and Digestive and Kidney Diseases (T32DK063929). All other authors report no disclosures relevant to the manuscript. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)

Background and Objectives: The prevalence of generalized joint hypermobility (GJH) is 5-65% in children and adolescents. The hypothesis of this study was to see whether there is an association between headache characteristics and GJH in children and adolescents with migraine., Methods: We performed a primary retrospective case-control analysis of an established database of patients with headache aged 5-17 years., Results: We included 5435 participants. Approximately 31.6% of participants (1,719/5,435) were diagnosed with GJH (Beighton score ≥ 6). Nausea (73.1% vs 67.5%, χ 2 with 1 degree of freedom = 17.0, p < 0.0001), phonophobia (87.3% vs 78.8%, χ 2 with 1 degree of freedom = 18.0, p < 0.0001), and the PedMIDAS score (48.2 ± 52.5, 95% CI 45.7-50.6 vs 41.6 ± 51.2, 95% CI 40.0-43.3, effect size = 0.13, p < 0.0001) were noted to be more severe in participants with GJH than those without GJH., Discussion: Youths with GJH and migraine were noted to have more severe migraine characteristics., Competing Interests: M. Samaha Kabbouche acted as a consultant for Theranica, AMGEN, Teva, and Lilly; was a PI/CoPI for Biohaven, and was a coinvestigator for the NIH. J. Kacperski has received research funding for participation in ongoing studies sponsored by Amgen, Eli-Lilly, Teva, Impax, Biohaven, Currax, Lundbeck, Upsher-Smith, and Curelator. All consulting and research funds for this work are paid directly to Cincinnati Children's Hospital Medical Center. This work does not affect the current presentation. Dr. Kacperski declares that there is no other potential conflict of interest. S. Powers provided scientific consulting for Theranica; received funding to his institution from the NIH and Patient-Centered Outcomes Research Institute; is an Associate Editor for Headache; is a Member of the Board of Directors for the American Headache Society; and provided grant reviews for the NIH and the Cystic Fibrosis Foundation. A.D. Hershey has received funds directly to his institution for advising and implementation of studies from Amgen, AbbVie, Lilly, Teva, Biohaven, Theranica, and Supernus and grant support from the NIH/NINDS and NICHDS. The other authors report no relevant disclosures., (© 2023 American Academy of Neurology.)

Background: Melatonin is effective for migraine prevention in adults. We hypothesized that melatonin would also be effective for migraine prevention in children and adolescents., Methods: This was a randomized, double-blind trial of melatonin (3 mg or 6 mg) versus placebo for migraine prevention in 10-17 year-olds with 4-28/28 headache days at baseline. Participants were recruited from the UCSF Child & Adolescent Headache Program, UCSF child neurology clinic, and social media advertisements. Migraine diagnosis was confirmed by a headache specialist. Participants completed an 8-week single-blind placebo run-in. Those meeting randomization criteria (≥4 headache days and ≥23/28 electronic diary entries during weeks 5-8) were randomized 1:1:1 to placebo:melatonin 3 mg:melatonin 6 mg nightly for 8 weeks. The primary outcome measure was migraine days in weeks 5-8 of randomized treatment between melatonin (combined 6 mg + 3 mg) versus placebo. We aimed to enroll n = 210., Results: The study closed early due to slow enrollment (n = 72). Two participants were in the single-blind phase when the study closed, therefore the meaningful n = 70. Sixteen percent (11/70) were lost to follow-up during the single-blind phase. An additional 21% (15/70) did not meet randomization criteria (<4 headache days: n = 5, <23/28 diary days: n = 7, both: n = 3). Sixty-three percent (44/70) were eligible to randomize, of whom 42 randomized (n = 14 per arm). Taking another preventive at enrollment (OR 8.3, 95% CI 1.01 to 68.9) was the only variable associated with meeting randomization criteria. Of those randomized, 91% (38/42) provided diary data in the final 4-weeks. However, given the amount of missing data, only those with ≥21/28 diary days were analyzed-7/14 (50%) in the placebo group, and 20/28 (71%) in the melatonin groups combined. Median (IQR) migraine/migrainous days in weeks 5-8 of double-blind treatment was 2 (1-7) in the placebo group versus 2 (1-12) in the melatonin groups combined; the difference in medians (95% CI for the difference) was 0 days (-9 to 3). There were no differences in adverse events between groups., Conclusions: When compared to recall at enrollment, headache days decreased across the single-blind placebo phase and the double-blind phase. There was no suggestion of superiority of melatonin; however, given the substantial portion of missing data, numerically higher in the placebo arm, and underpowering, this should not be interpreted as proof of inefficacy. Melatonin was generally well tolerated with no serious adverse events. Future migraine preventive trials in this age group may find this trial helpful for anticipating enrollment needs if using a single-blind placebo run-in. Enriching for those already on a migraine preventive may improve randomization rates in future trials, though would change the generalizability of results., (© 2023 American Headache Society.)

Background: Youth with continuous (always present) headache are vastly understudied; much remains to be understood regarding treatment response in this population., Objective: To describe and explore biopsychosocial factors related to initial clinical outcomes among treatment-seeking youth with continuous headache., Methods: This retrospective cohort study extracted data of 782 pediatric patients (i.e., aged <18 years) with continuous headache from a large clinical repository. Youth in this study had experienced continuous headache for ≥1 month before presenting to a multidisciplinary headache specialty clinic appointment. Extracted data from this appointment included patients' headache history, clinical diagnoses, and headache-related disability, as well as information about biopsychosocial factors implicated in headache management and/or maintenance (e.g., healthy lifestyle habits, history of feeling anxious or depressed). Additional data regarding patient headache characteristics, disability, and lifestyle habits were extracted from a subset of 529 youth who returned to clinic 4-16 weeks after their initial follow-up visit. After characterizing initial treatment response, exploratory analyses compared youth with the best and worst treatment outcomes on several potentially influential factors., Results: Approximately half of youth (280/526; 53.2%) continued to have continuous headache at follow-up, ~20% of youth (51/526) reported a significant (≥50%) reduction in headache frequency. Improvements in average headache severity (e.g., percentage with severe headaches at initial visit: 45.3% [354/771]; percentage with severe headaches at follow-up visit: 29.8% [156/524]) and headache-related disability were also observed (e.g., percentage severe disability at initial visit: 62.9% [490/779]; percentage severe disability at initial follow-up visit: 34.2% [181/529]). Individuals with the worst headache frequency and disability had a longer history of continuous headache (mean difference estimate = 5.76, p = 0.013) and worse initial disability than the best responders (χ 2 [3, 264] = 23.49, p < 0.001). They were also more likely to have new daily persistent headache (χ 2 [2, 264] = 12.61, p = 0.002), and were more likely to endorse feeling depressed (χ 2 [1, 260] = 11.46, p < 0.001)., Conclusion: A notable percentage of youth with continuous headache show initial improvements in headache status. Prospective, longitudinal research is needed to rigorously examine factors associated with continuous headache treatment response., (© 2023 American Headache Society.)

Objective: To examine group differences in self-reported migraine days among youth who completed the Childhood and Adolescent Migraine Prevention (CHAMP) trial prior to its closure and explore the relationship between self-reported and "nosology-derived" (i.e., International Classification of Headache Disorders, 3rd edition [ICHD-3]) migraine days., Background: The CHAMP trial compared amitriptyline and topiramate to placebo for migraine prevention in youth and proposed to analyze change in migraine days as a secondary outcome. There is considerable variability in the field regarding what constitutes a "migraine day," how this is determined and reported in trials, and how consistent these measures are with diagnostic nosology., Methods: CHAMP trial completers (N = 175) were randomized to receive amitriptyline (n = 77), topiramate (n = 63), or placebo (n = 35). Participants maintained daily headache diaries where they reported each day with headache and if they considered that headache to be a migraine. For each headache day, participants completed a symptom record and reported about symptoms such as pain location(s) and presence of nausea/vomiting or photophobia and phonophobia. We examined group differences in self-reported migraine days at trial completion (summed from trial weeks 20-24) compared to baseline. We also used an algorithm to determine whether participants' symptom reports met ICHD-3 criteria for migraine without aura, and examined the association between self-reported and "nosology-derived" migraine days., Results: Results showed no significant differences between groups in self-reported migraine days over the course of the trial. Self-reported and "nosology-derived" migraine days during the baseline and treatment phases were strongly associated (r's = 0.73 and 0.83, respectively; p's < 0.001)., Conclusion: Regardless of treatment, CHAMP trial completers showed clinically important reductions in self-reported migraine days over the course of the trial (about 3.8 days less). The strong association between self-reported and "nosology-derived" migraine days suggests youth with migraine can recognize a day with migraine and reliably report their headache features and symptoms. Greater rigor and transparency in the calculation and reporting of migraine days in trials is needed., (© 2023 American Headache Society.)

Background: Collaborations amongst researchers and clinicians with complementary areas of expertise enhance knowledge for everyone and can lead to new discoveries. To facilitate these interactions, shared language and a general understanding of how colleagues in different subfields of headache and headache research approach their work are needed., Methods: This narrative review focuses on research methods applied in animal studies, human studies including clinical trials, and provides an overview of clinical practice., Results: For animal studies, we describe concepts needed to evaluate the quality and relevance of preclinical studies. For human research, fundamental concepts of neuroimaging, quantitative sensory testing, genetic and epidemiological research methods, and clinical research methodology that are commonly used in headache research are summarized. In addition, we provide an understanding of what guides headache clinicians, and summarize the practical approach to migraine management in adults and children., Conclusions: It is hoped that this review facilitates further dialogue between clinicians and researchers that will help guide future research efforts and implementation of research findings into clinical practice., (© 2023 American Headache Society.)

Objective: 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., Background: 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., Methods: 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., Results: 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)., Conclusions: 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., (© 2022 American Headache Society.)

Objective: Examine preventive medication adherence among youth with migraine., Methods: Adherence (self-report, pill count, and blood serum drug levels) was assessed as an ancillary study that utilized data from 328 CHAMP Study participants (ages 8-17). CHAMP was a multisite trial of preventive medications. Participants completed a prospective headache diary during a six-month active treatment period during which youth took amitriptyline, topiramate, or placebo pill twice daily. Self-reported medication adherence was collected via daily diary. At monthly study visits, pill count measures were captured. At trial month 3 (trial midpoint) and 6 (end of active trial), blood serum drug levels were obtained. Self-report and pill count adherence percentages were calculated for the active trial period, at each monthly study visit, and in the days prior to participants' mid-trial blood draw. Percentages of nonzero drug levels were calculated to assess blood serum drug level data. Adherence measures were compared and assessed in context of several sociodemographic factors. Multiple regression analyses investigated medication adherence as a predictor of headache outcomes., Results: Self-report and pill count adherence rates were high (over 90%) and sustained over the course of the trial period. Serum drug level adherence rates were somewhat lower and decreased significantly (from 84% to 76%) across the trial period [t (198) = 3.23, p = .001]. Adherence measures did not predict headache days at trial end; trial midpoint serum drug levels predicted headache-related disability., Conclusions: Youth with migraine can demonstrate and sustain relatively high levels of medication adherence over the course of a clinical trial., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of Competing Interest All authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2021 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

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. 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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

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.

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., (© 2021 American Headache Society.)

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 < 0.001; effect size: d = 1.40). No differences between the groups were found for pain intensity and unpleasantness ratings of cold-water immersion nor the CPM response., Conclusions: This study found altered ascending nociceptive processing of mechanical stimuli at the neck in adolescents with migraine. However, endogenous pain modulatory mechanisms were functional and not altered. In light of other studies, impairments in inhibitory control may not be involved in migraine pathophysiology in pediatric patients regardless of stimulus location., (© 2020 American Headache Society.)

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 min (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 < 0.0001). More frequent PMR use was associated with a higher odds of headache free days (p = 0.0148)., Conclusion: Smartphone-based PMR introduced to patients who present to the ED for migraine is feasible and acceptable. More frequent users have more headache free days. Future work should focus on intervention engagement., (Copyright © 2020. Published by Elsevier Inc.)

Abstract: 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., (Copyright © 2020 International Association for the Study of Pain.)

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.

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)