Clinical outcomes in hemophilia: Towards development of a core set of standardized outcome measures for research

Introduction: A lack of uniformity in the choice of outcome measurement in hemophilia care and research has led to studies with incomparable results. We identified a need to define core outcome measures for use in research and clinical care of persons with hemophilia. Objective: To move toward a core set of outcome measures for the assessment of persons with hemophilia in research and practice. Methods: A modified nominal groups process was conducted with an international group of hemophilia experts, including persons with hemophilia as follows. Step 1: item generation for all potential outcome measures. Step 2: survey where respondents voted on the relative importance and usefulness of each item. Steps 3/4: 2-day meeting where attendees voted for items they valued, followed by open discussion and a second round of voting. Step 5: survey where respondents selected their top five items from those with >50% agreement at the meeting. Results: The highest ranked items for the pediatric core set (% agreement) are treatment satisfaction (92.7%), joint health (83.3%), a measure of access to treatment (82.5%), a measure of treatment adherence (72.5%), and generic performance based physical function (72.1%). The highest ranked items for the adult core set (% agreement) are total bleeding events (88.1%), EuroQol five dimensions (85.4%), treatment adherence (82.1%), joint health (79.1%), and number/location of bleeds per unit time (78.6%). Conclusion: This process generated a list of preferred outcome measures to consider for assessment in persons with hemophilia. This information now requires refinement to define optimal core sets for use in different clinical/research contexts

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 hospitaliza-tion), 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 presen-tation; 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

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

A wearable activity tracker intervention for promoting physical activity in adolescents with juvenile idiopathic arthritis: a pilot study

Abstract Background Children and adolescents with juvenile idiopathic arthritis (JIA) are less physically active than their healthy peers and are at high risk of missing out on the general health benefits of physical activity. Wearable activity trackers are a promising option for intervening in this population with potential advantages over traditional exercise prescriptions. The objectives of this study were to: (1) determine the feasibility of a wearable activity tracker intervention in adolescents with JIA; and (2) estimate the variability in response to a wearable activity tracker intervention on the physical activity levels of adolescents with JIA. Methods Participants aged 12–18 years with JIA were recruited during their routine rheumatology clinic visits at a tertiary care hospital. Participants completed the 3-Day Physical Activity Recall self-reported questionnaire at baseline, 1 week and 5 week follow-up. At the 1 week follow up, participants were instructed to start wearing an activity tracker for 28 consecutive days. Participants completed a feasibility questionnaire at their end of study visit. Participant demographics, adherence rates and feasibility outcomes were summarized using descriptive statistics. The effect of wearing a tracker on moderate-to-vigorous physical activity (MVPA) and total metabolic equivalents (METs) per day were analyzed using a paired t-test. Results Twenty-eight participants (74% female; median age 15.1, range 12.8–18.6) were included in the analysis. All of the participants were able to synchronize the activity tracker to a supported device, use the activity tracker correctly and complete the study measurements. On average, participants had activity logged on their smartphone application for 72% of the intervention period. The standard deviation of the change in mean METs/day was 12.148 and for mean MVPA blocks/day was 3.143 over the study period. Conclusion Wrist worn activity tracking is a feasible intervention for adolescent patients with JIA. More research is needed to examine the effect of activity tracking on physical activity levels. Trial Registration Not an applicable clinical device trial as per the criteria listed on ClinicalTrials.gov as the primary objective is feasibility

Updating the Canadian Hemophilia Outcomes–Kids’ Life Assessment Tool (CHO‐KLAT) in the era of extended half‐life clotting factor concentrates

Abstract 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

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