There was significant heterogeneity in the use of instruments across studies included within this systematic review. Multiple studies measured pain intensity, function and quality of life constructs; however fatigue was measured in only one study, which found it to be an independent predictor of functional deterioration. All measures used demonstrated change over time.
The identified PRO measures used similar item sets without taking into account lifestyle or severity of the condition. This limits their translational capabilities into clinical practice. Despite the advantage of assessing the same outcome repeatedly in a clinical trial for research, measuring changes in symptoms tailored to the child’s individual presentation may be more beneficial to inform clinical decisions (36). Children with GJH and associated symptoms commonly describe variable symptoms depending on their lifestyles, environmental condition or individual characteristics (37). The use of PROs with more inclusive questions that capture all relevant domains to an individual and their specific condition may provide a more useful alternative to better assist clinicians translate evidence into practice. Furthermore, the use of measures specifically validated for children with GJH and associated symptoms, would provide more robust evidence for the effectiveness of interventions in this patient population.
Therapy aims to improve quality of life and reduce disability in children with GJH and associated symptoms (38). It is unknown if generic outcome measures alone would enable reporting with adequate validity and sensitivity (39, 40). In this present review, the majority of studies administered multiple instruments, combining both PRO and CRO scales. Further evaluation with qualitative methodology may provide valuable insight into the priorities and needs of children with GJH and associated symptoms, and their caregivers. This may refine the constructs and specific outcome measures used in future research and clinical practice.
Consistent use of measures across studies of children with GJH and associated symptoms, ideally with a clear diagnostic label, would allow for informed assessment of therapy effectiveness. Lack of standardisation, together with the limited number of interventional or prospective cohort studies, has hampered quantitative synthesis of efficacy of interventions using meta-analysis in previous systematic reviews (23,24). In other paediatric rheumatological health conditions, such as Juvenile Idiopathic Arthritis (JIA), established and revised core sets of outcomes determined through expert health professional consensus (41, 42) have been used. In line with the findings of our review, the JIA international workgroup prioritised pain, function and quality of life (overall wellbeing) as mandatory domains for research. In addition, fatigue prioritised by patient/parents was considered an important construct outcome measure for inclusion in the most recent update (42).
There is a substantial impact of fatigue on quality of life of children with GJH and associated symptoms (15, 19, 20, 43, 44). The most poorly functioning children diagnosed with hypermobility and associated symptoms experience worse fatigue and higher pain intensity than their peers (32). No single assessment instrument has been identified to measure the severity of fatigue and its impact on wellbeing in this population group. Given the significance of fatigue, strong consideration of fatigue measurement is recommended within a core set of outcome measures.
Studies have also reported children and parents describing systemic symptoms such as gastrointestinal involvement and stress incontinence associated with poorer quality of life relating to hypermobility (15, 45, 46). Outcome measures measure that identify the impact of different systemic symptoms on child function and quality of life may also be useful to guide clinical management and assess the efficacy of interventions in this population.
This review was strengthened through the registration of a protocol, adherence to established PRISMA guidelines, and appraisal of methodological quality using a tool with substantial inter-rater reliability (47), and one that highlighted for use in assessing the quality of non-randomised controlled studies (48). We acknowledge a number of limitations to this review. The research strategy used within this review only identified studies published in English despite no language restrictions placed on eligibility criteria. Additionally, it was not the aim of the review to assess the validity or reliability of the included measures in the paediatric or condition-specific population.