Chronic Non-bacterial Osteomyelitis (CNO), also known as Chronic Recurrent Multifocal Osteomyelitis (CRMO), is an auto inflammatory bone condition that causes persistent bone pain, poor growth, and complications such as vertebral compression fracture. Understanding the possible epidemiological risk factors impacting the disease will provide all physicians including pediatric rheumatologists a better comprehension of the disease when diagnosing and treating CNO. The objectives of this study are to: 1) determine the annual incidence rate of CNO from King County; 2) compare the time to diagnosis from 2000-2019.Subjects were identified by the patient list maintained within Division of Rheumatology, Seattle Children’s Hospital. Diagnosis will be ascertained by chart review upon IRB approval based on published diagnostic criteria. Demographic and basic clinical information including the date of disease onset and physician diagnosis, first visit to a rheumatologist, and geographic location will be extracted. Public census data from King County will be used to calculate the annual incidence rate of CNO. Descriptive statistics will be performed and a nonparametric test will be used to determine the difference of time to diagnosis over time. A geographic mapping across WWAMI region for all cases will be generated to identify any patterns of case clustering. 250 subjects were identified with diagnosis of CNO between 2000 and 2019. Chart extraction will be completed after IRB approval. I expect the annual incidence rate calculated based on recent years (2015-2019) will be similar or greater than previously reported. I expect that the time to diagnosis is shortened during recent years likely due to the rise of awareness of CNO. From a large single center in the United States, I will be able to estimate the annual incidence rate of CNO in children. Continuous efforts of raising the awareness of CNO are needed to identify all cases for optimal care.

Hydrocephalus is a condition in which the cerebrospinal fluid (CSF) accumulates in the brain, increasing pressure inside the skull. A common method of treatment in pediatric patients is the placement of a shunt inside the fluid-filled ventricle of the brain. Overtime, shunts will become obstructed, fail to work, and require brain surgery and reimplantation of a new shunt. We will apply a intense focus ultrasound to send a pulse through the catheters obstructed by astrocyte tissue cultures in a three-dimensional model for shunt failure. When the method has been refined, we plan to apply ultrasound on catheters clogged from cerebrospinal fluid (CSF) that will be obtained from shunt replacement surgeries performed at Seattle Children’s hospital. Our aim is to improve the flow rate through the catheter, thus providing a less invasive method for shunt clearing in pediatric patients with hydrocephalus.

Chronic nonbacterial osteomyelitis (CNO) is an inflammatory disease that causes bone destruction, persistent pain and potential pathological fracture. Physical and laboratory findings are often unremarkable. Pain score is confounded by amplified pain syndrome in some children. Patient/parent reported outcome measurements (PROMIS) have been validated in healthy children but not in children with CNO to provide possible comprehensive and accurate assessment of disease activity. We aim to validate these measurements in a prospective, longitudinal cohort study, the Chronic nonbacterial Osteomyelitis International Registry (CHOIR). After IRB approval (#1232), children with a diagnosis of CNO were enrolled to the study with parental consents. Questionnaires including 7 pediatric PROMIS short forms and childhood health assessment questionnaire (CHAQ) were administered to subjects (7 or older) or parents (under 7) at each visit. Clinical assessment including physician global score (PGA) as well as demographic information were collected. PROMIS adjusted score were calculated through HealthMeasures Scoring Service. PGA and patient/parent global assessment of disease activity will be used as references to determine the validity of of each PROMIS form and CHAQ through nonparametric tests. 136 subjects were enrolled to the study from eight centers between June 2018 and January 2020. The rate of pediatric patients who took the surveys during their visits and the completion rate of answered questionnaires were calculated. This is the first study aiming to validate PROMIS pediatric forms in children with CNO. Data collected from Pediatric PROMIS® questionnaires will compliment other findings in research studies to estimate disease burden and response to treatments in children with CNO.

Adolescents with newly diagnosed T1D are at risk for poor physical and psychosocial outcomes. We explored associations between glycemic control (A1C) with diabetes-distress, resilience, and psychosocial comorbidities (e.g., depression) over the first five years of diagnosis. Adolescents, aged 10-17, with newly diagnosed T1D completed validated diabetes-distress and resilience scales one-year post-diagnosis. Psychosocial comorbidities and A1C were extracted from patient charts for 5-years from diagnosis, and A1C values were averaged per year. Regression analyses were used to investigate associations between resilience, diabetes-distress and psychosocial comorbidities with A1C. A1C was assessed annually up to five years post-diagnosis. At one-year post-diagnosis, N=60 adolescents (M=13.22±2.09 years) completed distress (M=27.97±7.01) and resilience scales (M=40.35±17.10). Average A1C at 1-year was 7.73± 1.57 and at 5-years was 8.78 ±1.92. 14% of the sample had at least one psychosocial comorbidity at diagnosis. Between years 1-5 post diagnosis, 28.6% of the sample had at least one comorbidity. The most common comorbidities were depression and anxiety. Diabetes-distress was associated with average A1C in the second year (F(1,29)=4.397, p=.045, R2=.132), third year, (F(1,27)=6.596, p=.016, R2=.196), fourth year, (F(1,24)=10.196, p=.004, R2=.298), and fifth year post-diagnosis (F(1,19)=10.665, p=.004, R2=.360). Resilience was associated with average A1C in the second year (F(1,29)=6.848, p=.014, R2=.191) and fifth years (F(1,19)=4.790, p=.041, R2=.201) post-diagnosis. Total psychosocial comorbidities at diagnosis was associated with average A1C in the second year (F(1,49)=2.209, p<.01), third year (F(1,45)=7.925, p<.01), and fifth year (F(1,28)=7.919, p<.01) post diagnosis. The first year of diagnosis for adolescents with T1D is crucial for detecting patients who are at a higher risk for developing poorer health outcomes. Adolescents who present with psychosocial comorbidities at diagnosis and report poor resilience and high distress one year later are at risk for subsequent poor glycemic control. 

Previous studies show that when a parent moves their infant to a second sleep location at night, it is often less safe than the original location. The objectives of this study were to assess the safety of infant second sleep locations consistent with the American Academy of Pediatrics Safe Sleep recommendations and analyze demographic factors associated with the occurrence of second sleep locations. We conducted a self-report survey of 1500 randomly selected parents with children <12 months using Qualtrics, an online survey platform. Questions focused on participant’s recent infant sleep behaviors, including sleep position, co-sleeping, and sleep location at 2 timepoints: sleep onset and after nighttime waking. We examined summary statistics of demographics for all participants and used T-tests and bivariate logistic regression to compare demographic characteristics of parents who reported a second sleep location with those who did not. Safe sleep was defined as: supine position, not co-sleeping, and in a crib, bassinet, or playard. A composite score examined if all safe sleep behaviors were used at both timepoints. We found that 39% of participants reported a second sleep location for their infant the previous night. Of parents who reported a second sleep location: 28% met all 3 safe sleep criteria at sleep onset, only 9% met all 3 criteria at both timepoints, and 66% of those parents did not meet the 3 criteria at either timepoint. Demographics associated with higher odds of reporting a second sleep location were parental age <29 years, Hispanic parents, preterm babies, first-time parents, babies <6 lbs, and parents identifying as the baby’s primary caretaker 6 days a week. Our findings show the prevalence of unsafe infant sleep behaviors used by parents throughout nighttime, highlighting a gap in our current approach to educating parents on safe sleep behaviors to minimize infant sleep mortality rates.

Executive function (EF), a broad term for an individual’s higher-order cognitive abilities, has been shown to be an important factor in proper development of play in childhood. Children with autism spectrum disorder (ASD) have been noted to score significantly lower on tasks requiring EF and are often noted to engage in more simplistic levels of play compared to typically developing peers. We investigated within-group associations of average play level for children with ASD, as observed during parent-child play sessions, in relation to parent-reported EF scores, as measured by the Behavior Rating Inventory of Executive Function (BRIEF). Participants with ASD (n = 28, age = 3-11 years) and participants with typical development (n = 27, age = 2-7 years) engaged in a video-recorded, 15-minute unscripted parent-child play session. Blind coders determined the child’s level of play, ranging from object manipulations to pretend play, on a numeric scale of 1-13. The highest level of play was coded at each one-minute epoch of engagement using Behavior Observation Research Interactive Software. Participant’s play scores were averaged and analyzed with their BRIEF scores using Pearson’s correlations. Results indicated no significant correlation between average play level and the BRIEF working memory, planning, and inhibition subscales, with Pearson’s correlations ranging from less than .01 to 0.03 (p > 0.8). Likewise, for participants with typical development, there was no correlation between average play level and BRIEF global composite scores, with Pearson’s correlations less than 0.01 (p > 0.9). Our current analysis did not account for parental support of the child’s play, which may contribute to why parent-reported EF scores did not relate to child play level in these unscripted parent-child play sessions. Future directions include examining the relationship between EF and play in children with other developmental disabilities.

Chronic Nonbacterial Osteomyelitis (CNO) is a severe and occult autoinflammatory bone disease of unknown cause. CNO predominantly affects children and young adults, with older literature reporting estimated annual incidence rates of 0.4 per 100,000 children. A timely diagnosis is challenging, but critical, because CNO may result in permanent bone damage, long-term disability, and disfigurement when left untreated. Diagnostic criteria were proposed by three groups. These sets of criteria were derived from single-center cohorts and none has been validated. In the proposed initiative, we developed a consensus among internationally recognized experts based on the analysis of a large international cohort of pediatric CNO patients and pediatric disease controls in order to develop and validate classification criteria for pediatric CNO. IRB approval was obtained at each site. CNO cases and mimicker cases were identified. Data were collected retrospectively using uniform case report form. The demographic, symptoms, physical examination, lab result and imaging feature were obtained. Descriptive statistics were performed. Our international group have collected a total of 360 cases including 226 CNO and 134 mimicker cases from 18 centers in 4 continents. 53% of subjects were females and 69% were whites. The typical site of bone pain is the lower extremity (231, 65%) followed by the lower torso (83, 24%). The most frequent imaging technique performed is the MRI (326, 91%). The top three mimicker diseases were infectious osteomyelitis (35, 10%), primary malignant bone disease (27, 8%) and juvenile idiopathic arthritis (24, 7%). The diagnosis of CNO was most commonly based on imaging features (116, 55%) and bone biopsies (61, 29%). A large international case repository was successfully created by using predetermined data collection form. These datasets can aid the development of classification criteria and future validation.

Chronic nonbacterial osteomyelitis (CNO) is a chronic autoinflammatory bone disease that typically affects children. It can cause complications such as bone deformities and vertebral fractures. Previous studies were retrospective in nature. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) CNO workgroup has created a consensus treatment plan for children with CNO refractory to NSAIDs and/or having spinal lesions. In order to determine the relative effectiveness of commonly used second-line medications, a longitudinal prospective study is needed. This study was approved by the Seattle Children’s Institutional Review Board (#1232). The CHronic nonbacterial Osteomyelitis International Registry (CHOIR) enrolls subjects under 21 years of age with a diagnosis of CNO, refractory to NSAID and/or having spinal lesions. The goal is to enroll 2000 patients and follow for at least 5 years. Demographic, clinical, laboratory, imaging data as well as patient/parent-reported outcomes were collected at baseline and follow up visits. 136 subjects were enrolled across 8 centers between June 2018 and January 2020, with 40 more centers anticipated to join. Data entry and data analysis are ongoing. We are presenting an inception cohort of over one hundred subjects. We expect that the longitudinal data will allow us to distinguish the responses from patients to different second-line medications. The patient/parent-reported outcomes are also expected to be an important component of the overall assessment. This is the first ever prospective longitudinal multicenter study on children with CNO. Results are expected to be highly applicable to improve clinical care.