Craig Frank Munns

Purpose: Perthes disease is a rare self-limiting avascular necrosis of the developing proximal capital femoral epiphysis. Identifying methods used to assess, diagnose and determine outcomes is essential to improve consistency in research and clinical care for this patient population. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews was used. Four electronic databases (Scopus, MEDLINE, CINAHL and Embase) were searched with articles included if clinical and radiological assessments were conducted on more than 10 participants, aged 0 to <18 years with Legg–Calvé–Perthes disease post 2004. Results: From 9145 records, 32 studies were included, identifying 16 clinical assessments, 23 radiological assessments, 10 diagnostic classifications and 22 outcome measures. Overall, 64% of outcome measures identified are not currently validated for children and adolescents. Conclusions: Substantial variability in the methods used to assess, diagnose and determine outcomes in children and adolescents with Perthes disease was identified. When coupled with limited use of validated paediatric measures, this inconsistency complicates clinical decision-making, reduces consistency in patient care and prevents comparability across studies. Establishing expert consensus to determine the most appropriate, accurate and child-specific measures is needed to enhance consistency in patient care, enable more robust outcome reporting and strengthen future research in Perthes disease. Significance of study: Significant variation in diagnostic, assessment and outcome measures for Perthes disease underscores the need for validated, child-specific tools to improve clinical decision-making, facilitate comparability across studies and strengthen future research. Level of evidence: Level III, scoping review

Cultured urine-derived cells (UDCs) have been proposed as a source of material for the RNA-based molecular diagnosis of genetic disorders. Previous studies have shown that UDCs can be clonally expanded, passaged, frozen, regrown and have some stem cell characteristics, but their anatomic origin and diagnostic utility remain insufficiently explored. In this study, we cultured UDCs from 40 individuals (aged 4 to 20 years; 21 females) and extracted RNA for sequencing. We compared UDC gene expression to that of marker genes of the kidney and urinary tract segments. UDC gene expression most closely matched marker genes of parietal epithelial cells that line the inner surface of Bowman’s capsule in the kidney glomerulus. UDCs expressed VCAM1 (CD106) and POUF51 (OCT4), consistent with a progenitor cell type. UDCs also expressed 54.4% of 3125 OMIM-listed disease-causing genes. This indicated that UDCs can be used to diagnose a similar number of genetic disorders as skin fibroblasts and a wider range of genetic disorders than can be analysed by RNA extracted from whole blood. In conclusion, UDCs are a non-invasive cell source for RNA sequencing that is suitable for investigating a broad range of conditions.

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To investigate the benefits and harms of surgical, non‐surgical, and pharmacological interventions for paediatric primary lower limb avascular necrosis (AVN). This is a common review protocol, outlining the approach for four separate Cochrane reviews for paediatric primary lower limb AVN. To assess the benefit and harm of surgical interventions for paediatric primary lower limb AVN on function, pain, patient‐reported outcomes, and radiological outcomes. To assess the benefit and harm of non‐surgical interventions for paediatric primary lower limb AVN on function, pain, patient‐reported outcomes, and radiological outcomes. To assess the benefit and harm of pharmacological interventions for paediatric primary lower limb AVN on function, pain, patient‐reported outcomes, and radiological outcomes. To assess the comparative effectiveness of surgical, non‐surgical, and pharmacological interventions for paediatric primary lower limb AVN on function, pain, patient‐reported outcomes, and radiological outcomes. The secondary objective for all four of the reviews is to evaluate health equity by assessing the effects across different geographical regions, gender, and age groups.

The number of patients with end‐stage kidney disease requiring haemodialysis (HD) is increasing worldwide, placing substantial pressure on healthcare systems. In Central Queensland, Australia, many patients, including Indigenous Australians, live far from major centres providing HD services. Teledialysis (Tele‐D), involving virtual nephrologist‐led ward rounds, can improve access to specialist care while supporting community‐based dialysis. This study evaluated the feasibility, safety and effectiveness of Tele‐D for satellite HD units in Central Queensland. This retrospective cohort study compared patients receiving in‐centre HD at Rockhampton Hospital (hospital group) with those receiving community HD (Tele‐D group), where dialysis nurses delivered routine care under a nephrologist‐led telehealth model comprising weekly virtual reviews via the Queensland Telehealth Portal and additional telephone or email support as required over a 2‐year period. Both groups received routine monthly pathology review and face‐to‐face outpatient review every 3 months. Clinical and biochemical outcomes, including haemoglobin, urea reduction ratio, albumin, calcium, phosphate and parathyroid hormone, showed no significant differences in longitudinal trajectories between groups. Haemoglobin levels in the Tele‐D group converged towards the recommended target range. Emergency department presentations, hospital length of stay and all‐cause mortality were lower in the Tele‐D group. However, after adjustment for age, sex, diabetes and modified Charlson comorbidity index (mCCI), the hazard ratio for mortality had a confidence interval crossing 1.0, indicating noninferiority rather than superiority. In this regional retrospective cohort, Tele‐D was feasible, with clinical, biochemical and survival outcomes comparable with conventional hospital‐based HD. Because patients in the Tele‐D group were younger, had fewer comorbidities and exclusively used arteriovenous fistulas for vascular access, causal inference cannot be made. These findings support the Tele‐D model of care and warrant further evaluation in larger prospective studies.

X-linked hypophosphatemia (XLH) is an X-linked dominant condition where fibroblast growth factor-23 (FGF23) excess leads to hypophosphatemic rickets, lower limb bowing, and musculoskeletal pain. Burosumab, a monoclonal antibody against FGF23, has been shown to ameliorate the clinical phenotype of XLH and has recently been approved for use in many countries. This study aimed to evaluate patient and parental/caregiver perception of burosumab therapy and the acceptability of current management practices in Australia. Children with XLH and parents/carers were invited to respond to a survey on clinical and management information including use of telehealth, access to multidisciplinary team members, and perceptions and experience regarding burosumab therapy. This was a multi-centre, cross-sectional survey-based study involving 4 tertiary Australian children’s hospitals. A total of 21 survey responses from parents/carers were received between December 2022 and October 2023. Mean (SD) age at time of survey was 12.7 (4.1) yr and median time on burosumab was 42 mo (range 2-100). Reported side effects of burosumab were limited to local skin reactions (38%, n = 8) and injection site pain (5%, n = 1), with the majority (62%, n = 13) reporting no side effects. Logistical issues (availability from the pharmacy or medical centre holiday closure) led to most instances of missed or delayed doses, which were reported by 24% (n = 5). Most participants reported seeing their specialist both face-to-face and via telehealth (64%, n = 14). The majority saw an endocrinologist (100%, n = 21) and orthopaedic surgeon (67%, n = 14), but only a small minority saw a psychologist (10%, n = 2). Answers to Likert scale questions revealed that most parents/carers and children reported a perceived improvement in physical and psychological symptoms and function with burosumab therapy. This study supports the use of recently published local guidelines to manage children with XLH on burosumab due to high satisfaction expressed by children and parents/carers. However, logistical issues leading to delayed or missed doses should be addressed.

Purpose: Autistic children have been shown to have poorer bone health than their non-autistic peers, but previous evidence on this topic has been based on small clinical samples and is limited by how bone health has been measured. The association between autism and bone health may also reflect confounding by correlated genetic or environmental factors, but prior studies have not addressed this issue. Methods: We address these issues using data from a population-representative cohort of Australian children with bone health measured by peripheral quantitative computed tomography (pQCT) for both children and parents. Data for 1,274 children (66 autistic, 1,208 non-autistic) aged 11–12 years (50% male) were drawn from the Child Health CheckPoint within the Longitudinal Study of Australian Children. pQCT measures at the tibial diaphysis (ankle) and metaphysis (shin) were recorded using an identical protocol for children and one attending parent. Child autism was parent reported. Regression analyses were used to compare differences between autistic and non-autistic children, and between parents of autistic children and parents of non-autistic children. Results: Our findings indicate poorer bone health as assessed by tibial pQCT among autistic children compared to non-autistic children at both the metaphysis and diaphysis. No differences in pQCT measures were found between parents of autistic and non-autistic children, suggesting no evidence of confounding by shared genetic or environmental factors. Conclusion: These findings reinforce the need to support improved bone development among autistic children and suggest that differences in bone health are likely driven by behavioural factors that are potentially amenable to intervention.

Objective To identify the types of conditions reported in peer-reviewed literature that result in chronic musculoskeletal lower limb pain in children and adolescents and explore the alignment of these conditions with the chronic pain reporting codes indexed in the International Classification of Diseases 11th Revision (ICD-11). Design This scoping review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources Five electronic databases were searched (Medline, EMBASE, PsycINFO, CINAHL and the Cochrane Library). Eligibility criteria Articles involving children and adolescents under 18 years and reporting on chronic musculoskeletal pain of the lower limb were included. Data extraction and synthesis We assigned an ICD-11 code to each condition based on details reported in the study. We recorded whether any of the presenting conditions were linked to an ICD-11 chronic pain manifestation code. Results From 12 343 records, 418 papers were included. There were 124 unique conditions associated with chronic lower limb pain, the most commonly reported being chronic widespread musculoskeletal pain (24 studies) and juvenile idiopathic arthritis (26 studies). Only 11.1% of presenting conditions were linked to an ICD-11 chronic pain manifestation code. Conclusion Most presenting conditions associated with chronic pain in the lower limb do not have a chronic pain manifestation code in the new global standard for recording health information. This means chronic pain associated with common lower limb conditions may remain invisible in global statistics.

Hypophosphatasia (HPP) is a rare, inherited, and systemic disorder characterized by impaired skeletal mineralization and low tissue nonspecific serum alkaline phosphatase (TNSALP) activity. It is caused by either autosomal recessive or dominant‐negative mutations in the gene that encodes TNSALP. The phenotype of HPP is very broad including abnormal bone mineralization, disturbances of calcium and phosphate metabolism, pain, recurrent fracture, short stature, respiratory impairment, developmental delay, tooth loss, seizures, and premature death. Other than supportive care, there has been no disease‐specific treatment available for those with HPP. Asfotase alfa is a fully humanized, recombinant enzyme replacement therapy for the management of HPP. It is available in several countries for the treatment of the more severe forms of HPP, namely perinatal and infantile HPP. This review will summarize the preclinical data on asfotase alfa and highlight the data from clinical trials and case reports. These data show the transformative nature of asfotase alfa when administered as part of an interdisciplinary treatment model.

Introduction It is well established that young people with moderate-severe (Gross Motor Function Classification System [GMFCS] levels II-V) cerebral palsy (CP) participate in less physical activity compared to typically developed peers, and children with CP who can walk without limitations (GMFCS level I). Frame Running (formerly RaceRunning) is a World Para Athletics sanctioned sport that allows people with moderate-severe CP to access, experience and compete in running using a specialised three-wheeled frame with low rolling resistance. The Run4Health pilot randomised controlled trial (protocol published elsewhere) was designed to investigate the cardiorespiratory benefits of a 12-week frame running training program in young people with CP (aged 8-21 years, GMFCS II-V). Following enrolment of 12 participants in the pilot study, additional funding was secured to expand the Run4Health study to include additional training/study sites, new research questions and outcome measures, based on feedback from consumers. Such changes necessitate an expanded and updated study protocol. This expanded Run4Health study will investigate the effects of a 12- week Frame Running training program on cardiorespiratory health, bone mineral density, gross motor function and capacity, physical activity participation, sleep, pain and quality of life in children and youth (aged 8-21 years) with moderate-severe CP (GMFCS levels II-V). Methods and Analysis One hundred and two children and youth with CP (age 8-21 years) classified in GMFCS levels II-V will be recruited across three sites (six training locations) and randomised to receive either 12 weeks of Frame Running training twice weekly for 60 minutes, or 12 weeks of usual care (waitlist control group). Outcomes will be measured at baseline, immediately post-intervention, and 12 weeks post-intervention. The control group will receive the intervention following T3, and have an additional assessment session following 12 weeks of training (T4). Outcomes include cardiorespiratory fitness, bone mineral density, blood pressure, habitual physical activity, body mass index, waist circumference, percentage body fat, gross motor function and capacity, community participation, sleep, pain, quality of life and mood, health utility, feasibility, tolerability, and safety. Adverse events will be monitored, and participants, caregivers and coaches will be interviewed to explore barriers and facilitators to ongoing, sustainable participation in Frame Running. Ethics and Dissemination Ethical approval for this study was granted by The Children’s Health Queensland Hospital and Health Service (HREC/21/QCHQ/69281) and the University of Queensland Human Research Ethics Committees (2021/HE000725). Research outcomes will be disseminated via scientific conferences and publications in peer reviewed journals; to therapists and coaches through professional and athletic organisations; and to people with CP and their families. Registration Australian New Zealand Clinical Trials Registry number: ACTRN12621000317897