Disease activity trajectories in juvenile dermatomyositis from childhood to adulthood.

OBJECTIVES: To assess whether there are identifiable subgroups of disease activity trajectory in a population of juvenile dermatomyositis (JDM) patients-followed throughout childhood and into adulthood-and determine factors that predict those trajectory groupings. METHODS: This is a retrospective, longitudinal inception cohort of patients with idiopathic inflammatory myopathies, largely JDM. We sought to identify baseline factors that predict membership into different groups (latent classes) of disease activity trajectory. RESULTS: A total of 172 patients (64% females), with median age at diagnosis of 7.7 years, were analyzed. We studied 4,725 visits (1,471 patient-years). We identified 3 latent classes of longitudinal disease activity, as measured by the modified disease activity score (DASm), with distinct class trajectories predicted by DASm at baseline, and by the changes of DASm from either baseline to 3 months or baseline to 6 months (early response to therapy). In the analysis in which DASm at baseline and the changes of DASm from baseline to 6 months are included as predictors, Class 1 (10%) has persistently high disease activity, Class 2 (34%) is characterized by moderate disease activity, and Class 3 (56%) is characterized by individuals with a high early disease activity but an apparently good response to treatment and long-term low disease activity. CONCLUSION: High early disease activity, and treatment resistance in the first few months, predict a more chronic longitudinal course of JDM.

Patterns of joint damage in severe haemophilia A treated with prophylaxis.

OBJECTIVE: The primary objective of this study was to assess whether there are different patterns (classes) of joint health in young boys with severe haemophilia A (SHA) prescribed primary tailored prophylaxis. We also assessed whether age at first index joint bleed, blood group, FVIII gene abnormality variant, factor VIII trough level, first-year bleeding rate and adherence to the prescribed prophylaxis regimen significantly predicted joint damage trajectory, and thus class membership. METHODS: Using data collected prospectively as part of the Canadian Hemophilia Primary Prophylaxis Study (CHPS), we implemented a latent class growth mixture model technique to determine how many joint damage classes existed within the cohort. We used a multinomial logistic regression to predict the odds of class membership based on the above predictors. We fitted a survival model to assess whether there were differences in the rate of dose escalation across the groups. RESULTS: We identified three distinct classes of trajectory: persistently low, moderately increasing and rapidly increasing joint scores. By multinomial regression, we found that only age at first index joint bleed predicted rapidly increasing joint scores. The rapidly increasing joint score class group moved through dose escalation significantly faster than the other two groups. CONCLUSIONS: Using tailored prophylaxis, boys with SHA follow one of three joint health trajectories. By using knowledge of disease trajectories, clinicians may be able to adjust treatment according to a subject's predicted long-term joint health and institute cost-effective programmes of prophylaxis targeted at the individual subject level.

Measuring the impact of changing from standard half-life (SHL) to extended half-life (EHL) FVIII prophylaxis on health-related quality of life (HRQoL) in boys with moderate/severe haemophilia A: Lessons learned with the CHO-KLAT tool.

INTRODUCTION: In many countries, there is a shift from standard half-life (SHL) to extended half-life (EHL) clotting factor concentrates (CFCs). AIM: To describe the experience of switching from SHL to an EHL FVIII CFC and the impact of this on frequency of infusions, factor consumption, bleeding rates and HRQoL using the Canadian Hemophilia Kids' Life Assessment Tool (CHO-KLAT). METHODS: A retrospective chart review was conducted at a single haemophilia treatment centre in 2018 that included boys (ages: 4-18 years) with moderate/severe haemophilia A, without inhibitors, who switched from a SHL to an EHL FVIII CFC in the previous 2 years and for whom HRQoL data were available. RESULTS: The study cohort comprised 38 boys [mean (SD) age: 11.0 (3.4) years] with moderate (n = 5)/severe (n = 33) haemophilia A. The switch was associated with a 33% reduction in the number of weekly infusions from a median of 3.5 to 2.3 (P < .0001) and a 17% reduction in median FVIII consumption from 103 IU/kg/wk to 85.5 IU/kg/wk (P = .004). There was no significant change in annualized joint bleed rates or in CHO-KLAT scores. CONCLUSIONS: Despite documenting several benefits of switching to EHL FVIII (less infusions, lower factor consumption with no increase in bleeding), our study did not demonstrate any improvement in HRQoL. We conclude that either the current CHO-KLAT tool is not optimized to measure burden of treatment administration in boys with low bleed rates switching from SHL to EHL FVIII CFCs or that a reduction of 1.2 infusions/week does not result in a meaningful change in HRQoL.

Use of ultrasound for assessment of musculoskeletal disease in persons with haemophilia: Results of an International Prophylaxis Study Group global survey.

AIM: The objective of this survey was to understand the global trends of imaging assessments in persons with haemophilia, focusing on point-of-care ultrasound (POCUS). Insights into the barriers impeding its widespread proliferation as a frontline imaging modality were obtained. METHODS: The survey opened in September of 2017 and closed in May of 2018. Haemophilia Treatment Centres (HTCs) treating both paediatric/adult patients were the population of interest. A REDCap survey of 25 questions was disseminated to 232 clinical staff in 26 countries. RESULTS: The majority of respondents (88.3%, 91/103) reported that POCUS is most useful to confirm or rule out a presumed acute joint bleed. European HTCs reported the highest routine use of POCUS at 59.5% (22/37) followed by HTCs in the "Other" countries of the world at 46.7% (7/15) and North American HTCs at 43.9% (25/57). At the time of the survey, physiotherapists were identified as the clinical staff who perform POCUS 52.8% (28/53) of the time, in contrast with nurses/nurse practitioners who represent only 5.7% (3/53) of users. The greatest perceived barriers to the implementation of POCUS are the lack of trained healthcare professionals who can perform POCUS at 69.2% (74/107) and the overall time commitment required at 68.2% (73/107). CONCLUSION: Despite POCUS being used in 49.5% (54/109) of sampled HTCs, it is still utilized almost 30% less globally than full diagnostic ultrasound. A list of barriers has been identified to inform HTCs which challenges they will likely need to overcome should they choose to incorporate this imaging modality into their practice.

Characterization of Primary IGF-1 Deficiency in a Cohort of Canadian Children with Short Stature Using a Novel Algorithm Tailored to Electronic Medical Records.

(1) Background: Severe primary insulin-like growth factor-I deficiency (SPIGFD) is a rare disorder causing short stature in children due to low insulin-like growth factor 1 (IGF-1) levels. Given the sparsity of reported cases of SPIGFD worldwide, the condition may be underdiagnosed, potentially preventing affected children from receiving therapy with recombinant human IGF-1 (rhIGF-1). Our objective was to determine the prevalence of SPIGFD among children with short stature at a large pediatric tertiary care center through the use of a novel electronic medical record (EMR) algorithm. (2) Methods: We queried our EMR using an algorithm that detected all children seen at our center between 1 November 2013 and 31 August 2021 with short stature and low IGF-1. We then conducted chart reviews, applying established diagnostic criteria for those identified with potential SPIGFD. (3) Results: From a cohort of 4863 children with short stature, our algorithm identified 30 (0.6%) patients with potential SPIGFD. Using chart reviews, we determined that none of these patients had SPIGFD. (4) Conclusions: Our algorithm can be used in other EMRs to identify which patients are likely to have SPIGFD and thus benefit from treatment with rhIGF-1. This model can be replicated for other rare diseases.

Burosumab for the treatment of cutaneous-skeletal hypophosphatemia syndrome.

Cutaneous-skeletal hypophosphatemia syndrome (CSHS) is a rare bone disorder featuring fibroblast growth factor-23 (FGF23)-mediated hypophosphatemic rickets. We report a 2-year, 10-month-old girl with CSHS treated with burosumab, a novel human monoclonal antibody targeting FGF23. This approach was associated with rickets healing, improvement in growth and lower limb deformity, and clinically significant benefit to her functional mobility and motor development. This case report provides evidence for the effective use of FGF23-neutralizing antibody therapy beyond the classic FGF23-mediated disorders of X-linked hypophosphatemia and tumor-induced osteomalacia.

Implementation and evaluation of a longitudinal diabetes educational programme for adolescents.

INTRODUCTION: International guidelines recommend structured and continuous educational programmes to expand diabetes knowledge and self-efficacy in youth. To address these recommendations within a paediatric diabetes clinic, we conducted a three-phase quality improvement project aimed at improving adolescents' confidence in diabetes self-management skills. METHODS: In phase 1, the Diabetes Learning Centre (DLC), an educational programme for adolescents with type 1 diabetes (T1D) ages 13-17 years, was developed and implemented. Programme feasibility was evaluated through programme attendance rates. Phase 2 aimed to guide ongoing programme development and optimisation. DLC attendees rated their baseline confidence in overall and individual T1D self-management skills on a 5-point Likert scale. Patient characteristics were summarised using descriptive statistics and the association between patient characteristics and overall confidence in T1D self-management was evaluated. Phase 3 used patient surveys to evaluate patient satisfaction and reported change in confidence in self-management skills following DLC attendance. RESULTS: In phase 1, 232 (81%) of eligible adolescents attended the DLC during the study period. In phase 2, median overall confidence in diabetes management on a Likert scale (0-4) was 3, representing 'quite confident', although confidence was low in some essential self-management skills. Higher confidence was associated with lower HbA1c (p<0.001). In phase 3, 77 (85%) of participants reported high levels of satisfaction with the DLC. 106 (82%) of completed worksheets were associated with improved confidence in the diabetes self-management skill addressed. CONCLUSIONS: Implementation of a longitudinal T1D educational model was feasible with good uptake in an existing T1D programme. While confidence at baseline was quite high for overall T1D self-management, it was low in some essential self-management skills, highlighting the need for this programme and specific educational gaps. Adolescents reported improvements in confidence and high levels of satisfaction following DLC attendance. Our model provides a replicable programme template to address longitudinal education needs.

Lengthening sleep reduces pain in childhood arthritis: a crossover randomised controlled trial.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a common chronic childhood disease and chronic pain is a debilitating feature. A strong link has been shown between poor sleep and pain in JIA. However, the causal direction is unknown. This study's aim was to determine if, in adolescents with JIA, a recommended healthful sleep duration leads to reductions in pain when compared with the restricted sleep (RS) duration that is commonly seen. METHODS: Patients with JIA (12-18 years old; pain score of ≥1 on a visual analogue scale) participated in a randomised, crossover sleep manipulation protocol. The 3-week protocol comprised a baseline week (BL), a week with healthy sleep duration (HSD; 9.5 hours in bed/night) and a RS week (RS; 6.5 hours in bed/night). After BL, participants were randomly assigned to either HSD or RS, and then crossed over to the other condition. Pain was self-assessed using the iCanCope with Pain app. We used Bayesian hierarchical models to estimate the effect of sleep duration on pain. RESULTS: Participants (n=31; mean age=15.0±1.8 years) averaged 1.4 (95% credible interval (CrI) 1.2-1.6) more hours of sleep per night during HSD relative to RS. Compared with RS, HSD resulted in a favourable effect on pain scores (OR 0.61, 95% CrI 0.39-0.95). CONCLUSION: It is possible to have adolescents with childhood arthritis get a healthier sleep duration, and this longer sleep results in reduced pain. These findings complement prior correlational studies and confirm a causal relationship between reduced sleep duration and increased pain. TRIAL REGISTRATION NUMBER: NCT04133662.

Teaching Adolescents With Type 1 Diabetes Self-Compassion (TADS) to Reduce Diabetes Distress: Protocol for a Randomized Controlled Trial.

BACKGROUND: Adolescents living with type 1 diabetes (T1D) often experience diabetes distress (DD), a construct distinct from depression or anxiety that refers to the negative emotions that arise from living with and managing diabetes. Self-compassion, which involves being open to one's own suffering and treating oneself with the same care one would show to loved ones, is associated with better psychological and clinical outcomes among individuals with T1D. Self-compassion is a skill that can be taught and therefore represents an opportunity for intervention. OBJECTIVE: The overall aim of this study is to assess the effectiveness of a web-based mindful self-compassion for teens (MSC-T) intervention on improving DD, anxiety, depression, diabetes-related disordered eating, and suicidal ideation experienced by youth with T1D (aged between 12 and 17 years) compared with a waitlist control group (standard of care). We will also explore (1) if the effect of the MSC-T intervention changes over time, (2) if the MSC-T intervention has a positive impact on measures of glycemic control, and (3) if the effect of the MSC-T intervention differs based on self-reported gender. METHODS: We will conduct a single-center, parallel-group randomized controlled trial of 140 adolescents with T1D followed for 12 months. Participants will be randomly allocated (using hidden allocation) in a 1:1 ratio to either the MSC-T intervention or the waitlist control group. Our primary outcome is DD, as measured by the Problem Areas in Diabetes-Teen (PAID-T) version at 3 months. Secondary outcomes, assessed at 3 and 12 months, include anxiety (Generalized Anxiety Disorder 7-item [GAD-7] scale), depression (Patient Health Questionnaire-9 [PHQ-9]), diabetes-related disordered eating (Diabetes Eating Problem Survey-Revised [DEPS-R] version), and suicidal ideation (using 1 question from the PHQ-9). RESULTS: Study recruitment began in October 2022 and was completed in March 2023, with a total of 141 participants enrolling. Data collection will be ongoing until March 2024. The first results are expected in June 2024. CONCLUSIONS: This study will be the first randomized trial to assess the effectiveness of the web-based MSC-T intervention on adolescents with T1D. Given that adolescence is a period where individuals are typically required to assume more responsibility for their diabetes care, providing adolescents with the tools they need to better manage the stress that often accompanies T1D management is paramount. TRIAL REGISTRATION: ClinicalTrials.gov NCT05463874; https://clinicaltrials.gov/study/NCT05463874. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53935.

The clinical features of juvenile dermatomyositis: A single-centre inception cohort.

INTRODUCTION: Juvenile Dermatomyositis (JDM), a severe and rare autoimmune disease, is the most common idiopathic inflammatory myopathy in children. We describe the clinical features of a large single-centre cohort. METHODS: We studied an inception cohort (0-18 years old) referred for diagnosis to the JDM clinic at The Hospital for Sick Children (SickKids), between January 1989 and September 2017. Probable or definite diagnosis of JDM was done according to the 2017 ACR/EULAR Criteria. We excluded children who had treatment started at another hospital. The data were collected retrospectively from clinical charts and the SickKids JDM database. RESULTS: 172/230 (74.8%) patients were included. They were most often female (female:male = 1.8:1); the age at diagnosis was 8.5±4.3 years. There was a positive family history for autoimmune disease in 52%, mainly rheumatoid arthritis. No patient died. The most common signs at inception were muscle weakness (85.5%), nailfold capillary abnormalities (83.4%), Gottron papules (78.5%), heliotrope rash (66.3%), abnormal gait (55.8%), and malar/facial rash (54.7%). The prevalence of Gottron papules, heliotrope rash, facial/malar rash, nailfold capillary abnormalities, Raynaud phenomenon, dysphonia/dysphagia (a frequent cause of hospitalization), mouth ulcers, calcinosis, eye problems, joint involvement, acanthosis nigricans and lipodystrophy increased during follow-up. Muscle enzymes, namely CK, ALT, AST, were often normal or only slightly raised despite active muscle disease; conversely LD was often high. Anti-Nuclear Autoantibodies were positive in 49.7% of patients at diagnosis. The course of the disease was: 29.1% monocyclic, 5.3% polycyclic, 33.1% chronic. The course of 56 patients (32.5%) was not classifiable due to length of follow-up. Corticosteroids were used as treatment in almost all our patients and 30% required intravenous therapy due to the severity of the presentation; methotrexate was added in 64%, more often in recent years. Unresponsive patients were treated mostly with intravenous immunoglobulins (IVIG). CONCLUSIONS: The information obtained from this relatively large number of patients adds to the growing knowledge base of this rare disease. TRIAL REGISTRATION: SickKids Research Ethics Board approved the study.

Early Abnormal Nailfold Capillary Changes Are Predictive of Calcinosis Development in Juvenile Dermatomyositis.

OBJECTIVE: The long-term outcomes of juvenile dermatomyositis (JDM) are more favorable in recent years. However, calcinosis is still among the complications that can cause serious functional impairment. Little is known about the pathogenesis and risk factors of calcinosis. The aim of this study is to determine risk factors for the development of calcinosis in JDM. METHODS: This was a single-center, retrospective cohort study. All patients were diagnosed and followed at the multidisciplinary JDM clinic of The Hospital for Sick Children, from January 1, 1989, until May 31, 2018. To investigate predictors of incident calcinosis, Cox regression analysis was performed. RESULTS: A total of 172 patients met inclusion criteria, with a median age at diagnosis of 7.7 years (IQR 4.9-12.1), and a median follow-up of 8.5 years (IQR 3.4-12.6, range 0.1-28.3). The only risk factor significantly associated with the development of calcinosis in the univariate analysis was nailfold abnormality at baseline (hazard ratio [HR] 4.86, P = 0.03). In multivariable analysis, including nailfold abnormality, age of diagnosis, sex, and duration from onset to diagnosis, the only statistically significant risk factor for calcinosis was the presence of nailfold abnormalities (HR 4.98, P = 0.03). Further, calcinosis was significantly increased in patients with a chronic course (chi-square 25.8, P < 0.001). CONCLUSION: The presence of abnormal nailfold capillary changes at baseline is predictive for the development of calcinosis in children with idiopathic inflammatory myopathies.

Feasibility of the wingate anaerobic exercise test as a clinical measure in patients with juvenile dermatomyositis.

BACKGROUND: Core sets, while widely adopted for clinical assessment in juvenile dermatomyositis (JDM), have some drawbacks - they are time consuming, were developed primarily for research, and require an experienced multidisciplinary team. We propose the Wingate Anaerobic Test, a 30-s all out test performed on a cycle ergometer, as a potential alternative; it is valid and reliable in this patient population. We aimed to determine the feasibility of performing the Wingate test as part of a typical clinic visit, and to determine if it is correlated to current measures of disease activity. METHODS: Patients 5-18 years of age, with JDM, were recruited from the JDM clinic at a large Canadian academic children's hospital. Participants underwent a standard clinic assessment, then completed a Wingate test at the end of the visit. RESULTS: Twenty-six patients participated in the study, representing a recruitment rate of 81%; of those, 88% were able to complete the Wingate test. Patients liked the Wingate test and felt it should be included as a regular clinic test. Absolute peak power (watts) on the Wingate test was strongly correlated to the manual muscle test (MMT-8) and the timed squat test. Relative peak power (watts/kg) on the Wingate test was strongly correlated to the timed squat test and the Childhood Myositis Assessment Scale (CMAS). Exploratory principal components analysis revealed that Wingate relative average power explained almost 2/3 of the variance of the CMAS, MMT and timed squats combined. CONCLUSION: The Wingate test is a feasible test for children with JDM and correlates well with standard clinical assessments. Given its brevity, it has the potential to replace more standard measures of physical function currently used in clinical assessments for children with JDM. Future work should focus on how best to operationalize Wingate testing in clinic without the use of dedicated personnel.

Comparing the Measurement Properties and Preferability of Patient-reported Outcome Measures in Pediatric Rheumatology: PROMIS vs CHAQ.

OBJECTIVE: The Childhood Health Assessment Questionnaire (CHAQ), though widely used for assessments in pediatric rheumatology, has drawbacks, including low correlation to disease activity and ceiling effects. We sought to determine if any tools from the Patient Reported Outcomes Measurement Information System (PROMIS) improve on these shortcomings and/or are preferred by patients. METHODS: Patients 5-17 years of age with juvenile idiopathic arthritis (JIA) or juvenile dermatomyositis (JDM) were recruited from the rheumatology clinics at a Canadian children's hospital. Participants completed the CHAQ, 3 PROMIS measures (pain interference, mobility, and physical activity), and underwent a standard clinical assessment. RESULTS: Fifty-two patients participated, 25 with JIA and 27 with JDM. None of the PROMIS measures suffered from ceiling effects, whereas the CHAQ Disability Index (DI) and pain visual analog scales both did, with 50% and 20% of patients achieving the best possible scores, respectively. The PROMIS mobility was moderately correlated to the CHAQ-DI (rs -0.60, 95% CI -0.75 to -0.40), and the PROMIS pain interference was strongly correlated to the CHAQ pain score (rs 0.65, 95% CI 0.43-0.80). No measures correlated with disease activity. Patients preferred the PROMIS to the CHAQ. CONCLUSION: The PROMIS pain interference, mobility, and physical activity measures improve in some areas where the CHAQ is weak: they do not suffer from ceiling effects, and patients prefer the PROMIS tools. More work is needed to determine the correlation and responsiveness of the PROMIS tools to changes in disease activity over time before they should be widely adopted for clinical use.

Correlation of a Modified Disease Activity Score (DAS) with the Validated Original DAS in Patients with Juvenile Dermatomyositis.

OBJECTIVE: Juvenile dermatomyositis (JDM) is a rare disease in children that is treatable, but patients may suffer from long-term effects. Clinical trials are needed to find better treatments for affected patients. Among validated tools for evaluating disease activity clinically is the Disease Activity Score (DAS), but it is not routinely collected in all clinics. We developed a modified DAS (DASmod), which can be scored using data routinely collected by our clinical staff and has been used in previous studies. The aim of this study was to determine if our DASmod correlates with the validated DAS in patients with JDM. METHODS: In this study, we used DASmod (scored 0-12) and DAS (scored 0-20) scores for patients with JDM in our clinic. We analyzed the correlation between the DASmod and the validated DAS. RESULTS: For 51 patients seen in our JDM clinic, the median (IQR) DASmod score was 2.0 (0-4.0) and the DAS score was 3.0 (0-5.5). Scores on the 2 tools were highly positively correlated (r = 0.94, P < 0.001, 95% CI 0.89-0.96). The linear regression was significant [R2 = 0.88, F (1, 49) = 357.60, P < 0.001] and in this dataset, the tools can be used interchangeably with the regression equation: DAS score = -0.26 + 1.5*DASmod. CONCLUSION: If the regression equation from this dataset is successfully tested against future datasets, then further research collaborations between centers that collect different data related to disease activity in children with JDM will be facilitated.

Updating the Canadian Hemophilia Outcomes-Kids' Life Assessment Tool (CHO-KLAT) in the era of extended half-life clotting factor concentrates.

INTRODUCTION: The purpose of this study was to review and update the content of the Canadian Hemophilia Outcomes-Kids' Life Assessment Tool version 2.0 (CHO-KLAT), in the context of extended half-life (EHL) factor concentrates (FCs) and to establish the validity and reliability of the updated CHO-KLAT. METHODS: Focus groups were conducted with boys with hemophilia, their parents, and health care providers across Canada to review the CHO-KLAT v2.0 and determine if any modifications were required. The validity of the revised CHO-KLAT (version 3.0) was then determined in a sample of boys with hemophilia and their parents by calculating its correlation with the Pediatric Quality of Life Core Module (PedsQL-Core). Test-retest reliability was assessed using an intraclass correlation coefficient (ICC). RESULTS: Thirteen focus groups at 5 pediatric hemophilia treatment centers (HTCs) (n = 71) resulted in 19 changes to the CHO-KLAT v2.0, generating a revised 40-item CHO-KLAT, the CHO-KLAT v3.0. Thirty-five boys with hemophilia (median age, 14; range, 7-17 years) and 47 parents participated in the validation of the CHO-KLAT v3.0. There was a moderate correlation between the CHO-KLAT v3.0 child self-report and PedsQL-Core (r = 0.56, P = .01), and a strong correlation between the CHO-KLAT v3.0 parent-proxy and PedsQL-Core (r = .79, P = .0007). The test-retest reliability ICC was 0.90 for the child self-report CHO-KLAT v3.0 and 0.68 for the parent-proxy CHO-KLAT v3.0. CONCLUSION: The CHO-KLAT v3.0 is a reliable and valid child-centric tool that effectively measures health-related quality of life in boys with hemophilia who are receiving standard half-life or EHL FCs.

Measuring the impact of hemophilia on families: Development of the Hemophilia Family Impact Tool (H-FIT).

INTRODUCTION: This study aimed to assess the impact of hemophilia on families, in the context of current and emerging hemostatic therapies, and explore the need for a hemophilia-specific tool targeted at parents of boys aged <4 years. A secondary aim was to develop and validate the new tool. METHODS: Focus groups were conducted with parents of boys with hemophilia and hemophilia health care providers at Canadian hemophilia treatment centers (HTCs) to review the relevance of the Pediatric Quality of Life Family Impact Module (PedsQL-FIM); a novel questionnaire was developed by identifying core themes expressed. This questionnaire, the Hemophilia Family Impact Tool (H-FIT) was validated in a sample of parents of boys with hemophilia relative to the PedsQL-FIM. RESULTS: Seven focus groups were conducted at four HTCs, generating themes specific to hemophilia not covered by the PedsQL-FIM, suggesting that a new tool be developed (the H-FIT). In the validation phase, 54 parents completed the H-FIT and PedsQL-FIM. The H-FIT had a strong correlation with the PedsQL-FIM across all ages (r = 0.79; P < .0001) and a moderate correlation for parents of boys aged <7 years (r = 0.64; P = .0007). There was a significant difference between the mean H-FIT scores for parents of boys using extended half-life factor (68.1; standard deviation [SD]=14.2) compared to standard half-life factor (54.7; SD=18.4; P = .04). CONCLUSION: A novel, disease-specific tool, the H-FIT, has been developed to measure the impact of hemophilia on families. The H-FIT has good preliminary measurement properties and may be responsive to changes in therapy associated with a decreased burden of administration.

The Effect of Creatine Supplementation on Muscle Function in Childhood Myositis: A Randomized, Double-blind, Placebo-controlled Feasibility Study.

OBJECTIVE: To evaluate the feasibility of studying creatine in juvenile dermatomyositis (JDM). Secondary objectives were to determine the effect of creatine on muscle function and metabolism, aerobic capacity, fatigue, physical activity, and quality of life (QOL), as well as its safety. METHODS: We conducted a 6-month, double-blind, randomized, multiple-baseline design; patients were assigned to creatine or placebo. Feasibility was assessed using attended study visits, completed study procedures, and adherence. Muscle function, aerobic capacity, and muscle strength were assessed with standardized exercise tests. Muscle metabolism was assessed using a 31-Phosphorus Magnetic Resonance Spectroscopy protocol. Fatigue, physical activity, and QOL were assessed by questionnaires. Statistical significance was estimated using a randomization (permutation) test. Changes in outcome measures taken at baseline and end-of-study were calculated using paired t-tests. RESULTS: Median (range) adherence to the study drug was 88.5% (20.5-95.5%) and the proportion of subjects with 80% adherence or higher was 76.9%. There were no missed study visits. There were no statistically significant changes in muscle function, strength, aerobic capacity, disease activity, fatigue, physical activity, or QOL while subjects were receiving creatine compared to placebo. There were statistically significant adaptations in muscle metabolism (e.g., decrease in change in muscle pH following exercise, and decrease in phosphate/phosphocreatine ratio) at the end-of-study compared to baseline. There were no significant adverse effects. CONCLUSION: Creatine supplementation in children with JDM is feasible to study, and is safe and well-tolerated; it may lead to improvements in muscle metabolism.

Magnetic resonance imaging in boys with severe hemophilia A: Serial and end-of-study findings from the Canadian Hemophilia Primary Prophylaxis Study.

BACKGROUND: This study examined the structural outcomes for joints of boys with severe hemophilia A receiving frequency/dose-escalated primary prophylaxis using magnetic resonance imaging (MRI), and the importance of interval MRI changes. METHODS: Forty-six subjects (27 with interval studies) were evaluated by radiographs (X-rays) and mid- and end-of-study MRIs (using the International Prophylaxis Study Group scale), as part of the Canadian Hemophilia Prophylaxis Study. The primary outcome was the presence of MRI osteochondral findings. RESULTS: The median (range) time on study at the end-of-study MRI examination was 9.6 (4.8-16.0) years, during which 18 of 46 subjects (39%) had osteochondral changes in at least one joint. An interval change in MRI score of at least 1 point was observed in 44% of joints (43 ankles, 21 elbows, 4 knees); at least one joint showed this change in all 27 subjects. Self-reported interval hemarthrosis was associated with a higher likelihood of interval osteochondral change (odds ratio [OR], 1.49; 95% confidence interval [CI] = 1.08-2.06). Presence of synovial hypertrophy or hemosiderin on interval MRIs was associated with an OR of 4.71 (95% CI, 1.92-11.57) and 5.25 (95% CI, 2.05-13.40) of later osteochondral changes on MRI. DISCUSSION: MRI changes were seen in 39% of subjects. Interval index joint bleeding was associated with an increased risk of later MRI changes, and earlier soft-tissue changes were associated with subsequent osteochondral changes.

Musculoskeletal ultrasound in hemophilia: Results and recommendations from a global survey and consensus meeting.

INTRODUCTION: For persons with hemophilia, optimization of joint outcomes is an important unmet need. The aim of this initiative was to determine use of ultrasound in evaluating arthropathy in persons with hemophilia, and to move toward consensus among hemophilia care providers regarding the preferred ultrasound protocols for global adaptation. METHODS: A global survey of hemophilia treatment centers was conducted that focused on understanding how and why ultrasound was being used and endeavored to move toward consensus definitions of both point-of-care musculoskeletal ultrasound (POC-MSKUS) and full diagnostic ultrasound, terminology to describe structures being assessed by ultrasound, and how these assessments should be interpreted. Next, an in-person meeting of an international group of hemophilia health care professionals and patient representatives was held, with the objective of achieving consensus regarding the acquisition and interpretation of POC-MSKUS and full diagnostic ultrasound for use in the assessment of musculoskeletal (MSK) pathologies in persons with hemophilia. RESULTS: The recommendations were that clear definitions of the types of ultrasound examinations should be adopted and that a standardized ultrasound scoring/measurement system should be developed, tested, and implemented. The scoring/measurement system should be tiered to allow for a range of complexity yet maintain the ability for comparison across levels. CONCLUSION: Ultrasound is an evolving technology increasingly used for the assessment of MSK outcomes in persons with hemophilia. As adoption increases globally for clinical care and research, it will become increasingly important to establish clear guidelines for image acquisition, interpretation, and reporting to ensure accuracy, consistency, and comparability across groups.