Acute Treatment of Migraine in Adolescents: Real-World Analysis of Remote Electrical Neuromodulation (REN).

Nearly 10% of children and adolescents in the United States experience migraine. Pharmacologic treatment of migraine in adolescents is limited due to only few US Food and Drug Administration (FDA)-approved medications, limited efficacy, or lack of tolerability. Remote Electrical Neuromodulation (REN) is a nonpharmacologic abortive treatment for migraine, cleared by the FDA for patients aged 12 years and above. This study evaluated real-world efficacy of REN in adolescents aged 12 to 17 years. Real-world data were collected from patients aged 12 to 17 years treated with the REN device (Nerivio) from January 1, 2021, to May 31, 2022. Study's end points included consistent efficacy two hours after treatment, use of REN as a standalone versus as an adjunct therapy, treatment intensity, and safety. Of 1629 adolescents included in the study, consistent response in at least 50% of treatments at two hours posttreatment was achieved by 60.3% of patients for pain relief, 26.3% for pain freedom, 66.3% for functional disability relief, and 41.2% for functional disability freedom. Of 2365 treatments in which medication usage was reported, REN was used as standalone therapy in 64.4% of the treatments, REN was combined with over-the-counter medications in 18.6%, and it was combined with prescription medications in 17%. Mean treatment intensity from 13,716 treatments was 28.5% (±13.6%) of the max stimulator output. Only three device-related adverse events were reported, all minor. This real-world analysis demonstrates the persistent efficacy of REN for abortive treatment of migraine in adolescents, extending findings of prior clinical trials in adolescents and real-world studies in adults.

Pharmacokinetic Evaluation of Intravenous Vitamin C: A Classic Pharmacokinetic Study.

PURPOSE: Intravenous vitamin C (IVC) is used in a variety of disorders with limited supporting pharmacokinetic data. Herein we report a pharmacokinetic study in healthy volunteers and cancer participants with IVC doses in the range of 1-100 g. METHODS: A pharmacokinetic study was conducted in 21 healthy volunteers and 12 oncology participants. Healthy participants received IVC infusions of 1-100 g; oncology participants received IVC infusions of 25-100 g. Serial blood and complete urine samples were collected pre-infusion and for 24 h post-infusion. Pharmacokinetic parameters were computed using noncompartmental methods. Adverse events were monitored during the study. RESULTS: In both cohorts, IVC exhibited first-order kinetics at doses up to 75 g. At 100 g, maximum concentration (Cmax) plateaued in both groups, whereas area under the concentration-time curve (AUC) only plateaued in the healthy group. IVC was primarily excreted through urine. No saturation of clearance was observed; however, the mean 24-h total IVC excretion in urine for all doses was lower in oncology participants (89% of dose) than in healthy participants at 100 g (99%). No significant adverse events were observed; thus, maximum tolerated dose (MTD) was not reached. CONCLUSION: IVC followed first-order pharmacokinetics up to 75 g and at up to 100 g had complete renal clearance in 24 h. IVC up to 100 g elicited no adverse effects or significant physiological/biochemical changes and appears to be safe. These data can be used to rectify existing misinformation and to guide future clinical trials. REGISTRATION: ClinicalTrials.gov identifier number NCT01833351.

Physician Perspectives on Acupuncture Use in the Pediatric Emergency Department.

OBJECTIVES: Acupuncture is a nonpharmalogical treatment modality that is used to treat pain. Prior research demonstrates that pediatric patients tolerate acupuncture well and patients may experience significant pain relief. The objectives of this study were to (1) explore the experiences of pediatric emergency department (ED) physicians as they used 2 acupuncture procedures, Battlefield Acupuncture and Four Gates procedures, and (2) describe factors impacting the feasibility of acupuncture implementation in the pediatric ED setting. METHODS: This qualitative study used individual semistructured interviews with pediatric emergency medicine physicians who had completed basic acupuncture training recruited using purposive sampling. Interviews were individually coded and analyzed using thematic analysis. RESULTS: Eight pediatric ED physicians participated in interviews. We identified multiple factors that promoted acupuncture use, multilevel barriers that impacted ED acupuncture implementation, offered multilevel solutions to overcome barriers to ED acupuncture implementation, and overall recommended continued use of ED acupuncture. Participants noted that education for patients, families, ED staff, and the general community may facilitate acupuncture implementation. To promote standardized and equitable access to acupuncture, participants recommended that all ED physicians in the division should be credentialed to provide acupuncture. In addition, participants recognized the benefits of an ED-specific electronic medical record documentation template and acupuncture toolbox including centralized acupuncture supplies, patient and family educational materials, and reference cards for physicians. CONCLUSIONS: Participants overall had positive experiences with ED acupuncture. Although multilevel barriers to use of acupuncture were noted, these may be mitigated by several strategies suggested by participants. Future research is needed to further explore the potential impact of these strategies, as well as examine clinical outcomes of acupuncture implementation in the pediatric ED setting.

Development and Assessment of an Abbreviated Acupuncture Curriculum for Pediatricians.

OBJECTIVE: Acupuncture has been shown to improve pain and other health outcomes in children and is well tolerated. However, use of acupuncture by pediatric medical providers is rare, in part due to the cost and time associated with formal training. We aimed to develop an abbreviated acupuncture curriculum and assess its impact and acceptability with academic pediatricians. METHODS: In this pilot study, pediatricians received instruction in 2 acupuncture protocols for treating acute and chronic pain (Battlefield Acupuncture and Four Gates) during a 10-hour course developed by board-certified medical acupuncturists. Learning methods included an online module with videos and articles, 2 live workshops, and additional home practice. Participants completed a skills-based exam and pre- and post-tests measuring knowledge and attitudes about acupuncture treatment. RESULTS: Forty-five physicians (divided among 3 cohorts) began the acupuncture training course, and 38 (84.4%) completed all components. The course significantly increased participants' perceived efficacy of acupuncture for acute and chronic pain. Participants showed significant improvement in acupuncture knowledge. All participants agreed that the course would influence their current medical practice, and all participants felt confident utilizing basic acupuncture. Additionally, all participants indicated that they would recommend the abbreviated acupuncture curriculum to a colleague. CONCLUSIONS: Pediatricians became proficient in 2 acupuncture protocols with a 10-hour curriculum and found the format and content highly acceptable. Future plans include studying acupuncture implementation and expanding the course to other departments and institutions.

Improving Acute Treatment of Pediatric Primary Headache Disorders With a Novel Headache Treatment Center: Retrospective Review of Preliminary Outcomes.

OBJECTIVE: To determine preliminary outcomes of targeted headache treatments provided at a novel outpatient acute care pediatric headache treatment center. BACKGROUND: Limitations exist in acute management of pediatric headaches, including inadequate access to specialty headache therapies and headache specialists in acute settings, variable success of emergency room treatments, and omission of comfort measures. An outpatient acute headache care clinic (the "Headache Treatment Center") was strategically initiated at a Midwestern pediatric academic hospital to provide acute and targeted headache therapies for children with active headaches. METHODS: We conducted a retrospective chart review of 154 visits from September through November 2018 of patients ages 7-18 years visiting the Headache Treatment Center. RESULTS: On average, headache intensity (measured on an 11-point pain numeric rating scale) decreased after interventions used in the Headache Treatment Center (mean change = 2.85 ± 2.81, P < .05, Cohen d = 1.01). Large effect sizes for reducing headache intensity were observed for pericranial, occipital/auriculotemporal, and occipital nerve blocks, Cohen d = 1.56, 1.64 and 1.02, respectively. Large effect sizes for reducing headache intensity also were observed for a transcutaneous supraorbital nerve stimulator device (Cefaly) (Cohen d = 1.02), acupuncture (Cohen d = 1.09), and intravenous migraine cocktails (Cohen d = 0.91-1.34). CONCLUSION: Targeted headache therapies to abort pediatric primary headaches as part of a novel headache clinic model may be beneficial for short-term management.

Integrative Management of Pediatric Primary Headaches.

Pediatric primary headache disorders are best treated using a comprehensive and integrative approach, due to the complex interactions between psychosocial and biological processes. Although more quality research is needed for treatment approaches to pediatric headaches, current practice management includes both pharmaceutical and nonpharmaceutical management. This article describes the integrative treatments used in a large regional pediatric headache program. Lifestyle approaches, nutraceuticals and dietary supplements, acupuncture, transcutaneous neurostimulation, relaxation, clinical hypnosis, biofeedback, and psychological services are discussed in detail for clinicians who may consider applying to their practice. [Pediatr Ann. 2019;48(6):e231-e235.].

Correction: Esparham, A., et al., Pediatric Integrative Medicine: Vision for the Future. Children, 2018, 5, 111.

The authors wish to make the following corrections to their paper [...].

Pediatric Integrative Medicine: Vision for the Future.

Pediatric integrative medicine (PIM) is of significant interest to patients, with 12% of the general pediatric population and up to 80% of children with chronic conditions using PIM approaches. The field of PIM has evolved over the past 25 years, approaching child health with a number of guiding principles: preventive, context-centered, relationship-based, personalized, participatory, and ecologically sustainable. This manuscript reviews important time points for the field of PIM and reports on a series of meetings of PIM leaders, aimed at assessing the state of the field and planning for its future. Efforts in the first decade of the 2000s led to increased visibility in academic and professional pediatric organizations and through international listservs, designed to link those interested in and practicing PIM, all of which continue to flourish. The PIM leadership summits in recent years resulted in specific goals to advance PIM further in the following key areas: research, clinical practice, professional education, patient and family education, and advocacy and partnerships. Additionally, goals were developed for greater expansion of PIM professional education, broader support for pediatric PIM research, and an expanded role for PIM approaches in the provision of pediatric care.

Pediatric Headache Clinic Model: Implementation of Integrative Therapies in Practice.

The demand for integrative medicine has risen in recent years as research has demonstrated the efficacy of such treatments. The public has also become more conscientious of the potential limitations of conventional treatment alone. Because primary headache syndromes are often the culmination of genetics, lifestyle, stress, trauma, and environmental factors, they are best treated with therapies that are equally multifaceted. The Children’s Mercy Hospital, Kansas City, Missouri Headache Clinic has successfully incorporated integrative therapies including nutraceuticals, acupuncture, aromatherapy, biofeedback, relaxation training, hypnosis, psychology services, and lifestyle recommendations for headache management. This paper provides a detailed review of the implementation of integrative therapies for headache treatment and discusses examples through case studies. It can serve as a model for other specialty settings intending to incorporate all evidenced-based practices, whether complementary or conventional.

Pediatric Integrative Medicine in Residency Program: Relationship between Lifestyle Behaviors and Burnout and Wellbeing Measures in First-Year Residents.

It is widely recognized that burnout is prevalent in medical culture and begins early in training. Studies show pediatricians and pediatric trainees experience burnout rates comparable to other specialties. Newly developed Accreditation Council for Graduate Medical Education (ACGME) core competencies in professionalism and personal development recognize the unacceptably high resident burnout rates and present an important opportunity for programs to improve residents experience throughout training. These competencies encourage healthy lifestyle practices and cultivation of self-awareness, self-regulation, empathy, mindfulness, and compassion—a paradigm shift from traditional medical training underpinned by a culture of unrealistic endurance and self-sacrifice. To date, few successful and sustainable programs in resident burnout prevention and wellness promotion have been described. The University of Arizona Center for Integrative Medicine Pediatric Integrative Medicine in Residency (PIMR) curriculum, developed in 2011, was designed in part to help pediatric programs meet new resident wellbeing requirements. The purpose of this paper is to detail levels of lifestyle behaviors, burnout, and wellbeing for the PIMR program’s first-year residents (N = 203), and to examine the impact of lifestyle behaviors on burnout and wellbeing. The potential of the PIMR to provide interventions addressing gaps in lifestyle behaviors with recognized association to burnout is discussed.

Pediatric Integrative Medicine.

The American Academy of Pediatrics is dedicated to optimizing the well-being of children and advancing family-centered health care. Related to this mission, the American Academy of Pediatrics recognizes the increasing use of complementary and integrative therapies for children and the subsequent need to provide reliable information and high-quality clinical resources to support pediatricians. This Clinical Report serves as an update to the original 2008 statement on complementary medicine. The range of complementary therapies is both extensive and diverse. Therefore, in-depth discussion of each therapy or product is beyond the scope of this report. Instead, our intentions are to define terms; describe epidemiology of use; outline common types of complementary therapies; review medicolegal, ethical, and research implications; review education and training for select providers of complementary therapies; provide educational resources; and suggest communication strategies for discussing complementary therapies with patients and families.

Mind-Body Therapy for Children with Attention-Deficit/Hyperactivity Disorder.

Attention-deficit/hyperactivity disorder (ADHD) is pervasive among the pediatric population and new treatments with minimal adverse effects are necessary to be studied. The purpose of this article is to review current research studying mind-body therapies for treatment of children diagnosed with ADHD. Literature was reviewed pertaining to the effectiveness of movement-based therapies and mindfulness/meditation-based therapies for ADHD. Many positive effects of yoga, Tai Chi, physical activity, and meditation may significantly improve symptoms of ADHD among children.

Nutritional and Metabolic Biomarkers in Autism Spectrum Disorders: An Exploratory Study.

CONTEXT: Autism spectrum disorder (ASD) is currently on the rise, now affecting approximately 1 in 68 children in the United States according to a 2010 surveillance summary from the Centers for Disease Control and Prevention (CDC). This figure is an estimated increase of 78% from the figure in 2002. The CDC suggests that more investigation is needed to understand this astounding increase in autism in such a short period. OBJECTIVE: The aim of this pilot study was to determine whether a group of children with ASD exhibited similar variations in a broad array of potential correlates, including medical histories, symptoms, genetics, and multiple nutritional and metabolic biomarkers. DESIGN: This study was a retrospective, descriptive chart review. SETTING: The study took place at the University of Kansas Medical Center (KUMC). PARTICIPANTS: Participants were 7 children with ASD who had sought treatment at the Integrative Medicine Clinic at the medical center. RESULTS: A majority of the children exhibited an elevated copper:zinc ratio and abnormal vitamin D levels. Children also demonstrated abnormal levels of the essential fatty acids: (1) α-linolenic acid (ALA)- C13:3W3, and (2) linoleic acid (LA)-C18:2W6; high levels of docosahexaenoic acid (DHA); and an elevated ω-6:ω-3 ratio. Three of 7 children demonstrated abnormal manganese levels. Children did not demonstrate elevated urine pyruvate or lactate but did have abnormal detoxification markers. Three of 7 patients demonstrated abnormalities in citric acid metabolites, bacterial metabolism, and fatty acid oxidation markers. A majority demonstrated elevated serum immunoglobulin G (IgG) antibodies to casein, egg whites, egg yolks, and peanuts. A majority had absent glutathione S-transferase (GSTM) at the 1p13.3 location, and 3 of 7 children were heterozygous for the glutathione S-transferase I105V (GSTP1). A majority also exhibited genetic polymorphism of the mitochondrial gene superoxide dismutase A16V (SOD2). CONCLUSIONS: The findings from this small group of children with ASD points to the existence of nutritional, metabolic, and genetic correlates of ASD. These factors appear to be important potential abnormalities that warrant a case control study to evaluate their reliability and validity as markers of ASD.

Pediatric Integrative Medicine Approaches to Attention Deficit Hyperactivity Disorder (ADHD).

Attention deficit hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in children and is increasing in prevalence. There has also been a related increase in prescribing stimulant medication despite some controversy whether ADHD medication makes a lasting difference in school performance or achievement. Families who are apprehensive about side effects and with concerns for efficacy of medication pursue integrative medicine as an alternative or adjunct to pharmacologic and cognitive behavioral treatment approaches. Integrative medicine incorporates evidence-based medicine, both conventional and complementary and alternative therapies, to deliver personalized care to the patient, emphasizing diet, nutrients, gut health, and environmental influences as a means to decrease symptoms associated with chronic disorders. Pediatric integrative medicine practitioners are increasing in number throughout the United States because of improvement in patient health outcomes. However, limited funding and poor research design interfere with generalizable treatment approaches utilizing integrative medicine. The use of research designs originally intended for drugs and procedures are not suitable for many integrative medicine approaches. This article serves to highlight integrative medicine approaches in use today for children with ADHD, including dietary therapies, nutritional supplements, environmental hygiene, and neurofeedback.

Comparison of the dose response to levalbuterol with and without pretreatment with S-albuterol after methacholine-induced bronchoconstriction.

STUDY OBJECTIVE: To determine the effect of S-albuterol on the dose response to levalbuterol in patients with moderate bronchoconstriction induced by a methacholine challenge. DESIGN: Prospective, randomized, double-blind, placebo-controlled, crossover study. SETTING: University-affiliated clinical trial center. PATIENTS: Twenty-two adults with mild, stable asthma. INTERVENTION: At the screening visit, patients were switched from their beta2-agonist to ipratropium bromide for use as an as-needed rescue therapy. At the baseline visit 2-6 days later, the provocative concentration of methacholine to induce a 30% decrease in forced expiratory volume in 1 second (FEV(1) PC(30)) was determined, followed by a nebulized racemic albuterol dose-response study with three doses of albuterol, to familiarize patients with the procedures. At visits 2 and 3, patients were randomly assigned to receive nebulized normal saline placebo or S-albuterol 5 mg before the methacholine challenge and were administered three escalating doses of levalbuterol after the challenge. MEASUREMENTS AND MAIN RESULTS: Area under the curve for FEV(1) over 40 minutes (AUC(0-40)) after administration of levalbuterol was the primary outcome, with slope of FEV(1) as the secondary outcome. In addition, the fraction of exhaled nitric oxide (FeNO) was measured before and after the challenges. In the 17 patients who met criteria for completion, no deleterious effect for S-albuterol was found for FEV(1) PC(30), AUC(0-40) FEV(1), or the FEV(1) slope(0-40). However, S-albuterol reduced the provocative concentration of methacholine to induce a 20% decrease in FEV(1) (PC(20) 0.52 +/- 2.06 vs 0.39 +/- 1.58 mg/ml, placebo vs S-albuterol, p=0.044) but did not affect FeNO. CONCLUSION: A single high dose of S-albuterol did not alter the bronchodilator response to levalbuterol. The effect on bronchial responsiveness requires further study.