New Medications Are Needed for Children With Juvenile Idiopathic Arthritis.

OBJECTIVE: To document the need for additional Food and Drug Administration (FDA)-approved medications for the treatment of juvenile idiopathic arthritis (JIA). METHODS: The electronic medical records of JIA patients treated at Cincinnati Children's Hospital Medical Center (CCHMC) and data from JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry were included in this study. Unmet medication need was defined in 2 ways: (a) the presence of chronically uncontrolled JIA, defined as a physician global assessment of JIA activity ≥3 (on a 0-10 scale, where 0 = inactive) OR ≥3 joints with active arthritis OR a patient global assessment of well-being ≥3 (on a 0-10 scale, where 0 = very well), despite sequential use of ≥2 biologic disease-modifying antirheumatic drugs (bDMARDs); and (b) the use of ≥1 bDMARD not approved for any JIA category. RESULTS: At CCHMC, 829 of 1,599 JIA patients (52%) were treated with ≥1 bDMARD, and 304 (19%) had been exposed to ≥1 unapproved bDMARD. In the CARRA Registry, 4,766 of 7,379 children (65%) had received ≥1 bDMARD, and 1,122 (15%) had been prescribed ≥1 unapproved bDMARD. Of those children treated with ≥2 bDMARDs for whom complete data were available, 52% (255 of 487) at CCHMC and 45% (527 of 1,159) in the CARRA Registry had chronically uncontrolled JIA despite the use of ≥2 bDMARDs. CONCLUSION: Despite the availability of bDMARDs currently approved for JIA, there is persistent need for additional therapies to control JIA signs and symptoms. Since FDA approval is critical to ensure access to bDMARDs, the study and licensing of new medications is critical to address the unmet medication need and to further improve JIA outcomes.

Patient perspectives on the linkage of health data for research: Insights from an online patient community questionnaire.

OBJECTIVE: To examine the patient perspective on the risks and benefits of linking existing data sources for research. MATERIALS AND METHODS: Between December 2015 and February 2016, we fielded a questionnaire in PatientsLikeMe, an online patient community representing over 2500 health conditions. The questionnaire was developed using subject matter expertise and patient feedback from a concept elicitation phase (N = 57 patients). The final questionnaire consisted of 37 items. RESULTS: Of n = 5741 who opened the email invitation, n = 3516 respondents completed the questionnaire (61.2%). Of these, 73.8% were women, 86.4% were Caucasian, 14.5% were 65 or older, and 44.9% had completed college or post-graduate education. Questionnaire respondents indicated that the most important benefits of sharing data were "helping my doctor make better decisions about my health" (94%) and "helping make new therapies available faster" (94%). The most important data sharing risk identified was health data being "stolen by hackers" (87%). Of 693 patients who were not comfortable with researchers accessing their de-identified data, most reported that their comfort levels would increase if they were able to learn how their data was protected (84%). In general, responders felt more comfortable when unique identifiers such as social security number (90%) and insurance ID (82%) were removed from the data for linkage and research use. DISCUSSION: The majority of patients in a US-based online community are comfortable with researchers accessing their de-identified data for research purposes. CONCLUSIONS: Developing methods to link databases minimizing the exposure of unique identifiers may improve patient comfort levels with linking data for research purposes.

Transition and transfer of the patient with paediatric-onset lupus: a practical approach for paediatric and adult rheumatology practices.

The prevalence of paediatric-onset SLE (pSLE) is estimated at 1million people worldwide and accounts for a significant proportion of SLE morbidity, mortality and cost. Patients with pSLE are especially vulnerable during and immediately following transfer from paediatric to adult rheumatology care, when substantial delays in care and increased disease activity are common. Transition is the process through which adolescents and young adults (AYA) develop the skills needed to succeed in the adult healthcare environment, a process that typically takes several years and may span a patient's time in paediatric and adult clinics. Recommendations for improving transition and transfer for AYA with pSLE include setting expectations of the AYA patient and family concerning transition and transfer, developing AYA's self-management skills, preparing an individualised transition plan that identifies a date for transfer, transferring at a time of medical and social stability, coordinating communication between the paediatric and adult rheumatologists (inclusive of both a medical summary and key social factors), and identifying a transition coordinator as a point person for care transfer and to monitor the AYA's arrival and retention in adult rheumatology care. Of paramount importance is empowering the adult rheumatologist with skills that enhance rapport with AYA patients, engage AYA patients and families in adult care models, promote adherence and encourage ongoing development of self-management skills.

Clinical Trial Design in Juvenile Idiopathic Arthritis.

Randomized clinical trials provide the gold standard evidence base to guide clinical practice. Despite major advances in trial design, pediatric clinical trials are still difficult to perform and pose unique challenges, including the need to consider the impact of developmental changes in trial design. Advances within pediatric rheumatology combined with the need to comply with legislative requirements have driven new approaches to performing pediatric clinical trials such as utilization of large research networks, incorporation of patient and family stakeholders in the planning and implementation of clinical trials, and the development of novel trial designs. The expansion of available biological therapeutics that now includes biosimilar drugs highlights the important and difficult balance of providing new and cost-effective drugs to children while ensuring safety in a vulnerable population. Future advances in juvenile idiopathic arthritis (JIA) clinical trials will likely be the application of precision medicine based on biologic, rather than phenotypic, classification of JIA, with improved understanding of pediatric clinical pharmacology. Clinical trial simulations and comparative effectiveness studies are important supplements to traditional clinical trials, permitting efficient studies and results that are more generalizable.

Missed opportunities for timely diagnosis of pediatric lupus in South Africa: a qualitative study.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is a serious multisystem autoimmune disease, which is more aggressive in children and people of African descent. In South Africa, pediatric SLE (pSLE) patients are at high risk for severe disease. Similar to pSLE worldwide, South African children and adolescents with SLE require subspecialized medical care. The aim of this study is to describe the care-seeking experiences of families and examine factors that contribute to delays in the diagnosis of pSLE. Specifically, we sought to identify factors to inform interventions that support the timely referral and diagnosis of pediatric SLE patients in South Africa. METHODS: In-depth, semi-structured interviews were conducted with 22 caregivers of pSLE patients recruited from two government hospitals in Cape Town, South Africa in 2014. Interviews were audio-recorded, transcribed, and analyzed for themes related to barriers to diagnosis. RESULTS: Six themes were identified and classified as either caregiver or health system barriers to diagnosis. Caregiver barriers included lack of knowledge regarding SLE, financial difficulties, and the social stigma of SLE. Health system barriers were lack of trained staff, a complex medical system, and misdiagnosis. CONCLUSION: Caregivers reported missed opportunities for diagnosing pSLE in their children. Raising public awareness may improve caregiver awareness and reduce stigma of pSLE. Improving family education at diagnosis holds potential to increase patient-physician trust and mitigate fear. Education modules for primary care providers at initial point of contact with the health care system may improve recognition of early pSLE and facilitate expedited referral to a specialist.

Prospective Mediation Models of Sleep, Pain, and Daily Function in Children With Arthritis Using Ecological Momentary Assessment.

OBJECTIVES: Sleep is an emerging area of concern in children with juvenile idiopathic arthritis (JIA). Research shows the presence of poor sleep quality and related adverse outcomes in pediatric pain populations, including JIA, but few studies have examined the prospective patterns of association between sleep and associated outcomes. This prospective study evaluated the direction and magnitude of associations between subjective sleep characteristics (sleep quality, difficulty initiating sleep, and sleep duration), pain intensity, and functional limitations in children with JIA. We hypothesized that pain intensity would partially mediate the relationship between sleep and functional limitations. METHODS: Children and adolescents with JIA (n=59; age range, 8 to 18 y) recruited during clinic visits, completed smartphone-based diaries for 1 month. Subjective sleep characteristics were reported each morning; pain and functioning were assessed 3 times daily. RESULTS: As hypothesized, the associations between sleep quality and functional limitations and between difficulty initiating sleep and functional limitations were partially mediated by pain intensity, at any given moment (z=-3.27, P=0.001, z=2.70, P<0.05). Mediation was not detected in a model testing the association between sleep duration, pain intensity, and functional limitations (z=-0.58, P=0.56). DISCUSSION: Results suggest that sleep is integral to understanding the momentary association between pain intensity and functioning in children with JIA.

Developing a standardized approach to the assessment of pain in children and youth presenting to pediatric rheumatology providers: a Delphi survey and consensus conference process followed by feasibility testing.

BACKGROUND: Pain in children with rheumatic conditions such as arthritis is common. However, there is currently no standardized method for the assessment of this pain in children presenting to pediatric rheumatologists. A more consistent and comprehensive approach is needed to effectively assess, treat and monitor pain outcomes in the pediatric rheumatology population. The objectives of this study were to: (a) develop consensus regarding a standardized pain assessment tool for use in pediatric rheumatology practice and (b) test the feasibility of three mediums (paper, laptop, and handheld-based applications) for administration. METHODS: In Phase 1, a 2-stage Delphi technique (pediatric rheumatologists and allied professionals) and consensus meeting (pediatric pain and rheumatology experts) were used to develop the self- and proxy-report pain measures. In Phase 2, 24 children aged 4-7 years (and their parents), and 77 youth, aged 8-18 years, with pain, were recruited during routine rheumatology clinic appointments and completed the pain measure using each medium (order randomly assigned). The participant's rheumatologist received a summary report prior to clinical assessment. Satisfaction surveys were completed by all participants. Descriptive statistics were used to describe the participant characteristics using means and standard deviations (for continuous variables) and frequencies and proportions (for categorical variables) RESULTS: Completing the measure using the handheld device took significantly longer for youth (M = 5.90 minutes) and parents (M = 7.00 minutes) compared to paper (M = 3.08 and 2.28 minutes respectively p = 0.001) and computer (M = 3.40 and 4.00 minutes respectively; p < 0.001). There was no difference in the number of missed responses between mediums for children or parents. For youth, the number of missed responses varied across mediums (p = 0.047) with the greatest number of missed responses occurring with the handheld device. Most children preferred the computer (65%, p = 0.008) and youth reported no preference between mediums (p = 0.307). Most physicians (60%) would recommend the computer summary over the paper questionnaire to a colleague. CONCLUSIONS: It is clinically feasible to implement a newly developed consensus-driven pain measure in pediatric rheumatology clinics using electronic or paper administration. Computer-based administration was most efficient for most users, but the medium employed in practice may depend on child age and economic and administrative factors.

Parent perceptions of child vulnerability are associated with functioning and health care use in children with chronic pain.

CONTEXT: The extent to which parent variables are associated with the level of disability experienced by children with persistent pain has been an area of increasing research. OBJECTIVES: To evaluate the extent to which parent perceptions of their child's vulnerability are associated with functioning and health care utilization among children with persistent pain. We also evaluated whether perceptions of child vulnerability contribute to an indirect relationship between parent distress and child functioning and/or child health care utilization. METHODS: The study sample comprised 87 patients aged 6-18 years and a parent attending a chronic pain clinic. Children completed questionnaires on functional limitations, and parents completed questionnaires on parent distress, perceptions of child vulnerability, and extent of the child's pain-related health care utilization. Hierarchical regression and bootstrapping mediation analyses were used to test study hypotheses. RESULTS: Perceptions of child vulnerability were found to be clinically elevated in nearly half (46%) of parents/caregivers, and average child functional ability for the sample was substantially lower than healthy norms. Parent perceptions of greater child vulnerability were significantly associated with poorer child functioning and more child pain-related health care utilization regardless of child age, sex, and duration of persistent pain. Parent distress was found to be indirectly related to child health care utilization through parent perceptions of child vulnerability but directly related to child functioning. CONCLUSION: Parent perceptions of child vulnerability appear important for understanding levels of child functional limitations and health care utilization among children with chronic pain.

A proposed framework to standardize the neurocognitive assessment of patients with pediatric systemic lupus erythematosus.

OBJECTIVE: To develop and propose a standardized battery of neuropsychological tests for the assessment of cognitive functioning of children and adolescents with pediatric systemic lupus erythematosus (SLE). METHODS: A committee of health care professionals involved in the assessment of pediatric SLE patients reviewed the literature to identify cognitive domains most commonly affected in pediatric SLE and in adult SLE. They then reviewed the standardized tests available for children and adolescents that assess the cognitive domains identified. Through a structured consensus formation process, the committee considered the psychometric characteristics and durations of the tests. RESULTS: A test battery was developed that appears suitable to provide a comprehensive assessment of cognitive domains commonly affected by pediatric SLE within a 2.5-hour period. CONCLUSION: It is hoped that the consistent use of this reliable and efficient battery increases the practicality of routine evaluations in pediatric SLE, enabling between-cohort comparisons and facilitating the longitudinal assessment of individual patients over time.

Assessment and management of pain syndromes and arthritis pain in children and adolescents.

Chronic musculoskeletal pain, whether it is idiopathic or disease-related, is common in childhood. Pediatric rheumatologists and other pediatric health care providers must understand the epidemiology of musculoskeletal pain as part of childhood, diagnose pain syndromes in children and rule out rheumatic disease, and be willing to initiate treatment of pain in children and adolescents. Practitioners' ability to carry out these tasks is enhanced by an awareness of the biopsychosocial model of pain, which integrates biologic, environmental, and cognitive behavioral mechanisms in describing the causes and maintenance of children's pain. A growing body of research in rheumatic diseases, such as JIA, and idiopathic musculoskeletal pain syndromes, such as JPFS, highlights the importance of environmental and cognitive behavioral influences in the pain experience of children in addition to the contribution of disease activity. These influences include factors innate in the child, such as emotional distress, daily stress, coping, and mood, and familial factors, such as parental psychologic health, parental pain history, and the nature of family interactions. Addressing these issues, while providing aggressive traditional medical management, optimizes pain treatment and improves overall quality of life for children who have musculoskeletal pain.

Treatment of pain in juvenile idiopathic arthritis: a survey of pediatric rheumatologists.

OBJECTIVE: To assess the opinions and current practice of pediatric rheumatologists regarding treatment of chronic pain in children with juvenile idiopathic arthritis (JIA). METHODS: Standardized questionnaires were distributed to pediatric rheumatologists who are members of the Children's Arthritis and Rheumatology Research Alliance. Demographic data, opinions, and attitudes were solicited about pain assessment, current treatment of JIA with residual pain, and actual use of opioids to treat pain in children with JIA. RESULTS: Of 99 rheumatologists who were contacted, 53 responses were received (53.5%). No significant demographic differences were found in attitudes about pain management and use of opioids. A total of 77.3% of respondents agreed that there are patients who continue to have significant pain despite adequate treatment. However, 59.6% disagreed with the use of opioid analgesics for treatment of those patients. Cross tabulations showed significant relationships between attitudes about opioid use and concerns for side effects, including drowsiness, fatigue, and constipation (chi(2) = 1.16, P > 0.05), as well as addiction (chi(2) = 5.51, P = 0.019). Thirty percent of those who strongly disagreed with opioid use and 52.4% of those who disagreed had in fact prescribed opioids in the past year. The most commonly prescribed opioids were codeine and oxycodone. Practitioners' perceived knowledge of the drugs significantly affected their likelihood to prescribe them. CONCLUSION: Pediatric rheumatologists are divided in their attitudes regarding treatment of residual pain in children with JIA. Concern for side effects appears to be a major factor in the decision to prescribe these analgesics. More data are needed to facilitate clearer cost-benefit analyses in the decision to prescribe opioids to this clinical population.