Combining Guided Intervention of Education and Relaxation (GIER) with Remote Electrical Neuromodulation (REN) in the Acute Treatment of Migraine.

BACKGROUND: Evidence indicates that combining behavioral treatments with pharmacological treatments for migraine prevention improves efficacy, but little is known about the outcomes of combining neuromodulation and behavioral interventions for acute treatment of migraine. Remote electrical neuromodulation (REN) is a U.S. Food and Drug Administration (FDA)-cleared nonpharmacological migraine treatment. The present study evaluated the clinical benefits of augmenting REN treatment with a specially tailored behavioral therapy consisting of Guided Intervention of Education and Relaxation (GIER) for the acute treatment of migraine. METHODS: In this two-arm observational study, real-world data were collected from patients across the United States who were using the REN device. Eighty-five migraine patients ≥18 years of age who treated their attacks with REN in parallel with the GIER intervention were individually matched on age and sex with 85 patients who used REN alone. The groups were compared on the proportion of migraine attacks in which they achieved pain relief, pain freedom, improvement of function, and return to normal function, all at 2 hours after treatment. RESULTS: Data from 170 users were analyzed (85 per group). Compared with the REN-only group, the REN+GIER group displayed a statistically significant higher proportion of patients achieving consistent pain relief (P = 0.008), consistent improvement in function (P = 0.014), and consistent return to normal function (P = 0.005), all at 2 hours after treatment. CONCLUSIONS: The results suggest that combining the GIER behavioral intervention with REN treatment can improve the therapeutic efficacy beyond that of REN alone, in terms of both pain level and improvement of disability.

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.

Randomized clinical trial of Fibromyalgia Integrative Training (FIT teens) for adolescents with juvenile fibromyalgia - Study design and protocol.

OBJECTIVE: Juvenile-onset fibromyalgia (JFM) is a chronic debilitating pain condition that negatively impacts physical, social and academic functioning. Cognitive-behavioral therapy (CBT) is beneficial in reducing functional disability among adolescents with JFM but has only a modest impact on pain reduction and does not improve physical exercise participation. This randomized controlled trial (RCT) aims to test whether a novel intervention that combines CBT with specialized neuromuscular exercise training (the Fibromyalgia Integrative Training program for Teens "FIT Teens") is superior to CBT alone or a graded aerobic exercise (GAE) program. DESIGN/METHODS: This 3-arm multi-site RCT will examine the efficacy of the FIT Teens intervention in reducing functional disability (primary outcome) and pain intensity (secondary outcome), relative to CBT or GAE. All interventions are 8-weeks (16 sessions) in duration and are delivered in small groups of 4-6 adolescents with JFM. A total of 420 participants are anticipated to be enrolled across seven sites with approximately equal allocation to each treatment arm. Functional disability and average pain intensity in the past week will be assessed at baseline, post-treatment and at 3-, 6-, 9- and 12-month follow-up. The 3-month follow-up is the primary endpoint to evaluate treatment efficacy; longitudinal assessments will determine maintenance of treatment gains. Changes in coping, fear of movement, biomechanical changes and physical fitness will also be evaluated. CONCLUSIONS: This multi-site RCT is designed to evaluate whether the combined FIT Teens intervention will have significantly greater effects on disability and pain reduction than CBT or GAE alone for youth with JFM. Clinical trials.gov registration: NCT03268421.

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.

The Influence of Lifestyle Factors on the Burden of Pediatric Migraine.

There is a gap in patient education and coaching of lifestyle factors related to pediatric migraine, which nurses are in a unique position to fill in order to provide comprehensive care to these patients. In order to help fill this gap, we conducted a targeted review of studies examining migraine and lifestyle factors in children and adolescents. Studies older than 2010, studies examining adults above the age of 18, studies not available in the English language, and secondary sources were excluded from the review. A final sample of 42 studies was included in this review. Lifestyle factors including stress, sleep, obesity, and diet were identified as playing a significant role in increasing the frequency, severity, and duration of migraine attacks in pediatric patients. Based on these findings, a framework is discussed for practical applications of this knowledge by nursing staff working in primary and specialty care clinics.

Enhancing Outpatient Dihydroergotamine Infusion With Interdisciplinary Care to Treat Refractory Pediatric Migraine: Preliminary Outcomes From the Comprehensive Aggressive Migraine Protocol ("CAMP").

OBJECTIVE: To determine preliminary outcomes of a treatment for refractory pediatric migraine that integrates outpatient dihydroergotamine (DHE) infusion with interdisciplinary adjunctive care. BACKGROUND: Limited data are available to inform treatment of refractory migraine in children. Intravenous DHE therapy has shown promise but has been implemented in costly inpatient settings and in isolation of nonpharmacological strategies shown to enhance analgesia and functional improvement. METHODS: We conducted a retrospective chart review of 36 patients ages 11-18 with refractory migraine who underwent a pilot treatment program in an outpatient neurology clinic. The treatment integrated up to 5 days of outpatient DHE infusion with adjunctive nonpharmacological care (pain coping skills training, massage, aromatherapy, and school reintegration support). Changes in headache, healthcare utilization, and functional limitations were assessed as indicators of treatment response through 3-month follow-up. RESULTS: On average, headache intensity declined (M = 5.8 ± 2.5 to M = 2.4 ± 2.7; P < .0001) during the treatment period and remained statistically significantly improved through 3-month follow-up. Headache frequency decreased by a mean of 1.5 days per week (M = 6.7 ± 1.0 vs M = 5.2 ± 2.7, P = .012) through 3-month follow-up, with a 27% reduction (from 0.91 to 0.66) in the proportion of patients reporting a continuous headache (P = .009). Over this same follow-up period, there was a reduction in school days missed per month (median [25th, 75th percentile]: 4.5 [0, 21.0] vs 0 [0.0, 0.5]). There also were reductions in headache-related visits per month to the emergency department and medical providers. Adverse effects were common but typically minor and transient. CONCLUSIONS: Combining outpatient DHE infusion with interdisciplinary adjunctive care has promise as an effective treatment option for adolescents with refractory migraine.

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.

Heterogeneous estrogen receptor expression in circulating tumor cells suggests diverse mechanisms of fulvestrant resistance.

Fulvestrant is a dose dependent selective estrogen receptor (ER) down-regulator (SERD) used in ER-positive metastatic breast cancer (MBC). Nearly all patients develop resistance. We performed molecular analysis of circulating tumor cells (CTC) to gain insight into fulvestrant resistance. Preclinical studies were performed with cultured breast cancer cells spiked into human blood and analyzed on the CellSearch(®) system. Clinical data are limited to a subset of patients with ER-positive MBC from a previously reported pilot trial whose disease was progressing on fulvestrant (N = 7) or aromatase inhibitors (AIs) (N = 10). CTCs were enumerated and phenotyped for ER and B-cell lymphoma (BCL2) using the CellSearch(®) CXC kit. In preclinical modeling, tamoxifen and AIs resulted in stabilized ER expression, whereas fulvestrant eliminated it. Five of seven patients progressing on fulvestrant had ≥5CTC/7.5 ml WB. Two of these five, treated with 500 mg/month fulvestrant, had no detectable CTC-expression of ER and BCL2 (an ER regulated gene). Three patients had heterogeneous CTC-ER and BCL2 expression indicating incomplete degradation of the ER target by fulvestrant. Two of these patients received 250 mg/month whereas the third patient received 500 mg/month fulvestrant. Her cancer harbored a mutation (Y537S) in the estrogen receptor alpha gene (ESR1). All seven ER positive patients progressing on AIs had heterogeneous CTC-ER expression. These results suggest heterogeneous mechanisms of resistance to fulvestrant, including insufficient dosage, ESR1 mutation, or conversion to dependence on non-ER pathways. CTC enumeration, phenotyping, and genotyping might identify patients who would benefit from fulvestrant dose escalation versus switching to alternative therapies.