Efficacy of aprepitant for refractory pruritus in patients with epidermolysis bullosa and atopic dermatitis: A retrospective study.

INTRODUCTION: At a single-center pediatric hospital, the neurokinin-1 receptor antagonist aprepitant was used to treat refractory pruritus in epidermolysis bullosa (EB) and atopic dermatitis (AD). METHODS: Thirty-seven patients were included (24 EB patients, 13 AD patients), ages 10 months to 37 years. RESULTS: 58% (14/24) of patients with EB and 85% (11/13) of patients with AD reported aprepitant was effective in decreasing their pruritus, with age-related differences in efficacy observed in EB patients, and access to the medication by insurance denial or availability of the drug as a barrier to use. CONCLUSIONS: Aprepitant shows promise in controlling refractory pruritus in pediatric EB and AD patients and deserves further study.

Healthcare utilization among youth with Ehlers-Danlos syndrome hypermobile type.

Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited disorders of connective tissue. EDS hypermobility type (EDS-HT), characterized by joint hypermobility, is most common and increasingly recognized in pediatrics. Treatment involves protecting joints, preventing injuries, and managing symptoms/comorbidities. Pediatric EDS-HT patients often see multiple medical providers; however, data on healthcare utilization (HCU) in this population are lacking. This retrospective, electronic chart review examines HCU data 1 year prior and subsequent to a new diagnosis of EDS-HT using Villefranche criteria. Demographics, diagnoses, and HCU (office visits, therapies, hospital encounters/procedures, and tests) were obtained for N = 102 youth attending a Connective Tissue Disorder Clinic over a 21-month timeframe. After EDS-HT diagnosis, HCU patterns shifted to reflect greater involvement of therapy (physical, psychological, and occupational) and symptom management. More genetics, rheumatology, and orthopedics visits occurred prediagnosis, and more physical therapy, pain management, cardiology, and neurology visits occurred postdiagnosis. Testing and hospital encounter/procedure frequencies did not change. Overall, the pattern of HCU changed from diagnostic to treatment, in accordance with evidence-based EDS-HT care. Understanding HCU patterns of pediatric patients with EDS-HT can elucidate patient interaction with the health care system, with the potential to inform and improve the standard of care.

Medical Management of Chronic Pancreatitis in Children: A Position Paper by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Pancreas Committee.

ABSTRACT: This position paper summarizes the current understanding of the medical management of chronic pancreatitis (CP) in children in light of the existing medical literature, incorporating recent advances in understanding of nutrition, pain, lifestyle considerations, and sequelae of CP. This article complements and is intended to integrate with parallel position papers on endoscopic and surgical aspects of CP in children. Concepts and controversies related to pancreatic enzyme replacement therapy (PERT), the use of antioxidants and other CP medical therapies are also reviewed. Highlights include inclusion of tools for medical decision-making for PERT, CP-related diabetes, and multimodal pain management (including an analgesia ladder). Gaps in our understanding of CP in children and avenues for further investigations are also reviewed.

In-hospital and 90-day outcomes after total pancreatectomy with islet autotransplantation for pediatric chronic and acute recurrent pancreatitis.

Total pancreatectomy with islet autotransplantation (TPIAT) is used to treat debilitating chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) that has failed medical and endoscopic therapy. We performed a retrospective review of TPIAT patients at a free-standing children's hospital to evaluate perioperative outcomes. Twenty patients (median age 13, 65% female) underwent TPIAT (2015 through 2017). Of the 20 patients, 95% had CP and 1 patient (5%) had ARP alone. Seventy-five percent of the patients had a pancreatitis-associated genetic mutation; 40% had pancreas divisum. The median surgical time was 757 (IQR 657 to 835) minutes. Median islet equivalents per kg of body weight (IEQ/kg) were 6404 (IQR 5018 to 7554). At 90 days postoperatively vs preoperatively, significantly fewer patients were receiving parenteral nutrition (0% vs 25%, P = .006) and opioids (45% vs 75%, P = .01). Short Form 36-Item Health Survey (SF-36) physical health module scores and total scores improved (34.0 preoperatively vs 54.6 at 90 days, P = .008, and 47.1 vs 65.3, P = .007, respectively); SF-10 physical health scores also improved (13.4 vs 33.1, P = .02). Insulin requirement decreased from 0.5 unit/kg/day to 0.4 unit/kg/day between discharge and 90 days (P = .02). TPIAT is an effective option when debilitating disease persists despite maximal medical and endoscopic therapy. Opioid, parenteral nutrition, and exogenous insulin use can successfully be weaned within 90 days after TPIAT, with gains in health-related quality of life.

Anxiety Adversely Impacts Response to Cognitive Behavioral Therapy in Children with Chronic Pain.

OBJECTIVE: To evaluate whether clinical anxiety in children presenting to a pediatric pain management center is associated with a poorer treatment response for those who completed pain-focused cognitive behavioral therapy (CBT). STUDY DESIGN: The total sample consisted of 175 children, 40 of whom completed CBT for chronic pain. The Screen for Child Anxiety Related Emotional Disorders was completed at initial evaluation and outcome measures (average pain intensity and the Functional Disability Inventory) were collected during the initial evaluation and at the end of CBT. Group differences in outcomes were examined following CBT. The role of anxiety in CBT initiation and completion was also explored. RESULTS: Presence of clinical anxiety was associated with greater initiation and/or completion of pain-focused CBT but also a poorer treatment response. Specifically, the group with subclinical anxiety exhibited a substantial reduction in pain intensity, and the group with clinical anxiety exhibited a more limited response to treatment (F [1, 36] = 13.68 P < .01). A similar effect was observed for Functional Disability Inventory, such that the group with clinical anxiety had a significantly smaller response to treatment (F [1, 38] = 4.33 P < .05). The difference in pain and disability between groups following CBT suggest moderate effects (Cohen d = 0.77 and 0.78, respectively). CONCLUSIONS: Although youths with clinical anxiety are more likely to start and/or complete pain-focused CBT, anxiety has an adverse impact on CBT treatment response in children with chronic pain. Identification of patients with anxiety and use of tailored behavioral interventions may improve clinical outcomes.

Pain care for patients with epidermolysis bullosa: best care practice guidelines.

BACKGROUND: Inherited epidermolysis bullosa (EB) comprises a group of rare disorders that have multi-system effects and patients present with a number of both acute and chronic pain care needs. Effects on quality of life are substantial. Pain and itching are burdensome daily problems. Experience with, and knowledge of, the best pain and itch care for these patients is minimal. Evidence-based best care practice guidelines are needed to establish a base of knowledge and practice for practitioners of many disciplines to improve the quality of life for both adult and pediatric patients with EB. METHODS: The process was begun at the request of Dystrophic Epidermolysis Bullosa Research Association International (DEBRA International), an organization dedicated to improvement of care, research and dissemination of knowledge for EB patients worldwide. An international panel of experts in pain and palliative care who have extensive experience caring for patients with EB was assembled. Literature was reviewed and systematically evaluated. For areas of care without direct evidence, clinically relevant literature was assessed, and rounds of consensus building were conducted. The process involved a face-to-face consensus meeting that involved a family representative and methodologist, as well as the panel of clinical experts. During development, EB family input was obtained and the document was reviewed by a wide variety of experts representing several disciplines related to the care of patients with EB. RESULTS: The first evidence-based care guidelines for the care of pain in EB were produced. The guidelines are clinically relevant for care of patients of all subtypes and ages, and apply to practitioners of all disciplines involved in the care of patients with EB. When the evidence suggests that the diagnosis or treatment of painful conditions differs between adults and children, it will be so noted. CONCLUSIONS: Evidence-based care guidelines are a means of standardizing optimal care for EB patients, whose disease is often times horrific in its effects on quality of life, and whose care is resource-intensive and difficult. The guideline development process also highlighted areas for research in order to improve further the evidence base for future care.

Child pain catastrophizing mediates the relation between parent responses to pain and disability in youth with functional abdominal pain.

OBJECTIVES: Functional abdominal pain (FAP) in youth is associated with substantial impairment in functioning, and prior research has shown that overprotective parent responses can heighten impairment. Little is known about how a range of parental behaviors (overprotection, minimizing, and/or encouragement) in response to their child's pain interact with child coping characteristics (eg, catastrophizing) to influence functioning in youth with FAP. In this study, it was hypothesized that the relation between parenting factors and child disability would be mediated by children's levels of maladaptive coping (ie, pain catastrophizing). METHODS: Seventy-five patients with FAP presenting to a pediatric pain clinic and their caregivers participated in the study. Youth completed measures of pain intensity (Numeric Rating Scale), pain catastrophizing (Pain Catastrophizing Scale), and disability (Functional Disability Inventory). Caregivers completed measures of parent pain catastrophizing (Pain Catastrophizing Scale), and parent responses to child pain behaviors (Adult Responses to Child Symptoms: Protection, Minimizing, and Encouragement/Monitoring subscales). RESULTS: Increased functional disability was significantly related to higher child pain intensity, increased child and parent pain catastrophizing, and higher levels of encouragement/monitoring and protection. Parent minimization was not related to disability. Child pain catastrophizing fully mediated the relation between parent encouragement/monitoring and disability and partially mediated the relation between parent protectiveness and disability. CONCLUSIONS: The impact of parenting behaviors in response to FAP on child disability is determined, in part, by the child's coping style. Findings highlight a more nuanced understanding of the parent-child interaction in determining pain-related disability levels, which should be taken into consideration in assessing and treating youth with FAP.

Radiation of pain: Psychophysical evidence for a population coding mechanism in humans.

The spread of pain across body locations remains poorly understood but may provide important insights into the encoding of sensory features of noxious stimuli by populations of neurons. In this psychophysical experiment, we hypothesized that more intense noxious stimuli would lead to spread of pain, but more intense light stimuli would not produce perceptual radiation. Fifty healthy volunteers (27 females, 23 males, ages 14-44) participated in this study wherein noxious stimuli (43, 45, 47 and 49°C) were applied to glabrous (hand) and hairy skin (forearm) skin with 5s and 10s durations. Also, visual stimuli displayed on the target bodily area were utilized as a control. Participants provided pain (and light) spatial extent ratings as well as pain (and light) intensity ratings. In the extent rating procedure, participants adjusted the extent of the square displayed on the screen with the extent of pain (or light) which they experienced. Pain extent ratings showed statistically significant radiation of pain indicated by 12.42× greater spatial spread of pain (pain extent) than the area of the stimulation with 49°C (p<0.001), in contrast to visual ratings which closely approximated the size of the stimulus (1.22×). Pain radiation was more pronounced in hairy than glabrous skin (p<0.05) and was more pronounced with longer stimulus duration (p<0.001). Pain intensity explained only 14% of the pain radiation variability. The relative independence of the pain radiation from pain intensity indicates that distinct components of population coding mechanisms may be involved in the spatial representation of pain versus intensity coding.

A narrative review of the literature on illness uncertainty in hypermobile ehlers-danlos syndrome: implications for research and clinical practice.

BACKGROUND: Hypermobile Ehlers-Danlos syndrome (hEDS) is characterized by joint and skin laxity, and often accompanied by chronic pain, dysautonomia, increased distress and, functional limitations. The journey to accurate diagnosis is often prolonged due to unclear etiology of symptoms. This manuscript is a narrative review of the literature on illness uncertainty (IU) in hEDS, highlighting the unique facets of IU in this population, as compared to the broader chronic pain population (given symptom overlap between these two disease groups), that warrant additional investigation. Additionally, we considered the unique challenges associated with IU in the context of the developmental nuances of pediatric populations. Specifically, we aimed to (1) map the extant literature of the IU experience in chronic pain conditions broadly including the pediatric and adult research to identify key concepts related to IU and incorporate potential developmental considerations in IU; (2) delineate and describe the IU experience specifically in patients with hEDS, with the goal of identifying gaps in the literature based on aspects of presentation in hEDS that do and do not differ from the broader chronic pain population; and (3) elucidate the potential areas of adverse impact of IU in both general chronic pain populations, and those with hEDS specifically, to provide actionable areas for future research and clinical care of individuals with hEDS. Results of this review indicate that IU has been well-studied in chronic pain generally, but inadequately evaluated in hEDS specifically. Specific features of hEDS (complexity of the disorder, involvement of multiple bodily systems, contribution of organic pathology) may uniquely contribute to IU in this population. This review suggests that ambiguities surrounding the diagnosis of hEDS, symptom course, and treatment recommendations, along with misdiagnosis, perceived dismissal of symptoms, or attribution of symptoms to mental health concerns might increase risk for IU and related distress in patients. CONCLUSION: Findings from the present review suggest that distinct features of hEDS yield a set of driving factors for IU that may be somewhat different than those faced by patients with chronic pain or other medical conditions. The development of a validated measure of IU to appropriately assess this construct in patients with hEDS is a research priority. In the clinical setting, providers should be attentive to the potentially aversive diagnostic and treatment experiences reported by patients and attempt to provide clear explanations based on the extant knowledge of hEDS, and implement best-practice recommendations for multidisciplinary treatment.

Development and evaluation of the patient-reported outcomes measurement information system (PROMIS) pediatric pain quality item bank and short form.

ABSTRACT: Pain is a common problem among children, particularly those with pediatric chronic diseases. Multifaceted assessment of pain can improve communication about pain and help clinicians characterize, differentiate, and treat a patient's unique experience of pain. Pain quality is an important domain of pain, describing the subjective sensory experiences associated with pain as well as the affective experiences of pain. The aim of the current study was to quantitatively evaluate the measurement properties of the 59 Patient-Reported Outcomes Measurement Information System pediatric pain quality candidate items developed as part of the National Institutes of Health's Patient-Reported Outcomes Measurement Information System initiative with input from children and adolescents with chronic pain. Participants included N = 448 pediatric patients between 8 and 18 years of age with chronic health conditions with a prominent component of chronic or recurrent pain, including juvenile fibromyalgia, juvenile idiopathic arthritis, and sickle cell disease. A confirmatory factor analysis revealed a unidimensional model fit the data best, with 56 of the 59 items demonstrating good psychometric properties for inclusion in the final measure. In addition, a consensus-building method was used to establish 2 versions of a short form measure-one with 8 items focused primarily on the sensory pain qualities and one with 8 items focused on affective pain qualities. The final measure shows good reliability and validity, and is recommended for use in research and clinical care with pediatric populations.

Case report: neurological complications associated with epidural analgesia in children: a report of 4 cases of ambiguous etiologies.

The safety and utility of pediatric epidural analgesia is well established, but the risk of permanent neurological injury is unknown and largely must be extrapolated from adult literature. In this article we present a series of 4 cases of longterm or permanent neurologic complications associated with epidural analgesia. Possible mechanisms of injury and implications for practice are discussed.

Complex regional pain syndrome in children: asking the right questions.

BACKGROUND: Complex regional pain syndrome (CRPS) is a painful disorder without a known unifying mechanism. There are little data on which to base evaluation and treatment decisions, and what data are available come from studies involving adults; however, even that literature is relatively sparse. Developing robust research for CRPS in children is essential for the progress toward optimal treatment. OBJECTIVES: To determine potential avenues of research in pediatric CRPS based on a review of the literature. Areas of concern include diagnostic criteria, peripheral mechanisms, central nervous system mechanisms, the role of the autonomic nervous system, possible risk factors, options for prevention and potential avenues of treatment. METHODS: A literature review was performed and the results applied to form the hypotheses posited in the form of research questions. RESULTS AND CONCLUSIONS: CRPS is a complicated entity that is more than a painful sensory condition. There is evidence for peripheral inflammatory and neurological changes, and reorganization in both sensory and motor cortexes. In addition, a significant motor component is frequently observed and there appear to be tangible risk factors. Many of these pieces of evidence suggest options for prevention, treatment and monitoring progress and outcome. Most of the data are derived from adult studies and need to be replicated in children. Furthermore, there may be factors unique to pediatrics due to developmental changes in neuroplasticity as well as somatic, endocrinological and emotional growth. Some of these developmental factors may shed light on the adult condition.

A guide to diagnoses, indications, and contraindications for interventions in pediatric chronic pain.

Although the painful conditions in children and young adults do not involve a broad spectrum of disorders, the treatment itself may pose a challenge. Taking care of psychosocial factors is equally important as taking care of physical aspects. Our simple suggestion is to start with basics and advance to more complex treatments if needed. Please review Figure 2 for suggested treatment algorithms.

Special considerations and recommendations for interventions for pediatric chronic pain.

In select cases, interventional pain management techniques can bean effective adjunct to the multidisciplinary care of pediatric patients with chronic pain. The secret to success stems in proper patient selection and in delineating clear goals and expectations­motivated patients do well. Comfort measures ranging from distraction through general anesthesia should be employed to alleviate anxiety and distress, and to provide optimal working conditions for the proceduralist. In the appropriate context, the occasion to provide interventional care can be a rewarding role for the anesthesiologist to play in chronic pediatric pain patient care.

Signature for Pain Recovery IN Teens (SPRINT): protocol for a multisite prospective signature study in chronic musculoskeletal pain.

INTRODUCTION: Current treatments for chronic musculoskeletal (MSK) pain are suboptimal. Discovery of robust prognostic markers separating patients who recover from patients with persistent pain and disability is critical for developing patient-specific treatment strategies and conceiving novel approaches that benefit all patients. Given that chronic pain is a biopsychosocial process, this study aims to discover and validate a robust prognostic signature that measures across multiple dimensions in the same adolescent patient cohort with a computational analysis pipeline. This will facilitate risk stratification in adolescent patients with chronic MSK pain and more resourceful allocation of patients to costly and potentially burdensome multidisciplinary pain treatment approaches. METHODS AND ANALYSIS: Here we describe a multi-institutional effort to collect, curate and analyse a high dimensional data set including epidemiological, psychometric, quantitative sensory, brain imaging and biological information collected over the course of 12 months. The aim of this effort is to derive a multivariate model with strong prognostic power regarding the clinical course of adolescent MSK pain and function. ETHICS AND DISSEMINATION: The study complies with the National Institutes of Health policy on the use of a single internal review board (sIRB) for multisite research, with Cincinnati Children's Hospital Medical Center Review Board as the reviewing IRB. Stanford's IRB is a relying IRB within the sIRB. As foreign institutions, the University of Toronto and The Hospital for Sick Children (SickKids) are overseen by their respective ethics boards. All participants provide signed informed consent. We are committed to open-access publication, so that patients, clinicians and scientists have access to the study data and the signature(s) derived. After findings are published, we will upload a limited data set for sharing with other investigators on applicable repositories. TRIAL REGISTRATION NUMBER: NCT04285112.

Development and Psychometric Evaluation of the PROMIS Pediatric Pain Intensity Measure in Children and Adolescents with Chronic Pain.

The goal of the current study was to enhance the measurement of the pediatric chronic pain experience through a methodologically rigorous approach. This paper outlines the development and initial validation of a pain intensity measure for pediatric patients with chronic pain using Patient-Reported Outcomes Measurement Information System methodology. Measure development incorporated feedback from children with painful conditions. Based on input from pediatric participants and content experts, 4 candidate items assessing pain intensity were included for large scale testing. Children completed self-report items pertaining to their pain experience that were developed as part of a larger pool of new candidate Patient-Reported Outcomes Measurement Information System pediatric pain domain items as well as measures of pain interference, depressive symptoms, fatigue, pain behavior, pain intensity, and pain catastrophizing. The final sample for the large scale testing included N = 442 pediatric patients between the ages 8 to 18 years (Mean age = 13.54, Standard Deviation = 2.78; 71.27% female) experiencing chronic pain. Psychometric analysis resulted in a final measure that included 3 items with evidence of reliability (Cronbach alpha = .82) and convergent validity. The Likert format of the response options may be preferable to the traditional numeric rating scale for use in pediatric populations who experience chronic pain based on patients' feedback, which was directly utilized in designing the scale. Further, the inclusion of fewer and clinically meaningful response options should reduce ambiguity for young respondents. PERSPECTIVE: We have developed and evaluated a clinically sensitive and psychometrically precise 3-item pain intensity measure with Likert-type responses for self-report use among children and adolescents ages 8 to 18 years with chronic pain. Development of the item content and response options included input from children and adolescents with chronic pain. The development of pain intensity items with pediatric appropriate language, and labeled, fewer response options to yield maximal clinically meaningful information improves the precision of pain intensity measurement in children.

Perioperative care of patients with epidermolysis bullosa: proceedings of the 5th international symposium on epidermolysis bullosa, Santiago Chile, December 4-6, 2008.

Epidermolysis bullosa (EB) has become recognized as a multisystem disorder that poses a number of pre-, intra-, and postoperative challenges. While anesthesiologists have long appreciated the potential difficult intubation in patients with EB, other systems can be affected by this disorder. Hematologic, cardiac, skeletal, gastrointestinal, nutritional, and metabolic deficiencies are foci of preoperative medical care, in addition to the airway concerns. Therefore, multidisciplinary planning for operative care is imperative. A multinational, interdisciplinary panel of experts assembled in Santiagio, Chile to review the best practices for perioperative care of patients with EB. This paper presents guidelines that represent a synthesis of evidence-based approaches and the expert consensus of this panel and are intended to aid physicians new to caring for patients with EB when operative management is indicated. With proper medical optimization and attention to detail in the operating room, patients with EB can have an uneventful perioperative course.

The Role of Neuraxial Opioids in Pediatric Practice.

Neuraxial-spinal and epidural-administration of opioids can be an effective method for controlling pain for children in a number of clinical settings. Understanding the basic pharmacologic and logistical concepts will make it easier for pediatricians to advocate for their patients, and support patients and families when circumstances suggest that neuraxial opioid treatment is appropriate. This review article summarizes the basic concepts of pharmacology, drug choice, side effects, and complications as well as situations in which neuraxial opioids are appropriate in children.