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Anterograde intraflagellar transport (IFT) trains are essential for cilia assembly and maintenance. These trains are formed of 22 IFT-A and IFT-B proteins that link structural and signaling cargos to microtubule motors for import into cilia. It remains unknown how the IFT-A/-B proteins are arranged into complexes and how these complexes polymerize into functional trains. Here we use in situ cryo-electron tomography of Chlamydomonas reinhardtii cilia and AlphaFold2 protein structure predictions to generate a molecular model of the entire anterograde train. We show how the conformations of both IFT-A and IFT-B are dependent on lateral interactions with neighboring repeats, suggesting that polymerization is required to cooperatively stabilize the complexes. Following three-dimensional classification, we reveal how IFT-B extends two flexible tethers to maintain a connection with IFT-A that can withstand the mechanical stresses present in actively beating cilia. Overall, our findings provide a framework for understanding the fundamental processes that govern cilia assembly. In situ cryo-electron tomography reveals the molecular structure of intraflagellar transport (IFT) protein complexes and their assembly into the anterograde IFT trains that build cilia.

Background Musculoskeletal (MSK) conditions are a major source of morbidity and disability. There is a lack of global comparable data on the burden of MSK conditions in children and young people. Our aim was to estimate the global prevalence of three MSK conditions - Talipes Equinovarus (Clubfoot), Juvenile Idiopathic Arthritis (JIA) and Juvenile Systemic Lupus Erythematosus (JSLE). Methods Using reported prevalence rates, age-stratified population data within the World Bank Data Bank in 2017 and United Nations country classification, we estimated the prevalence of these MSK conditions in < 5 year olds (clubfoot) and < 16 year olds (JIA and JSLE) across the world. Results We estimated that in 2017, there were ~ 675,061 < 5 year olds with clubfoot among 675,100,000 < 5 year olds, ~ 2,069,246 < 16 year olds with JIA and ~ 206,931 < 16 year olds with JSLE per 2,069,000,000 < 16 year olds, totalling ~ 2,951,238 with one of these conditions. Disease prevalence was greatest in Asia (South Asia), followed by Africa, Americas, Europe and Oceania. Conclusions An estimated 3 million children and young people globally are currently living with either clubfoot, JIA or JSLE; many in Asia and Africa. Further work is needed urgently to engage with global stakeholders to work together to improve access to effective care for the many who are affected and reduce the otherwise adverse lifelong impact on their health, quality of life and the impact on society.

Background The World Health Organisation Essential Medicines List (WHO EML) guides National Essential Medicines Lists and Standard Treatment Guidelines for clearly identified disease priorities especially in low- and middle-income countries. This study compares the degree to which the basket of medicines recommended for rheumatic diseases in children and young people in National Essential Medicines Lists of countries in the WHO Africa region, corresponds to the 2021 WHO EML and WHO EML for children, as a proxy of availability. Methods An online search of the WHO medicines and health technology portal, the Health Ministry websites of the 54 African countries, PUBMED and Google Scholar, with search terms for ‘National Essential Medicines List’, AND/OR ‘standard treatment guidelines’ AND/OR ‘Lista Nacional de Medicamentos Essenciais’ AND/ OR ‘Liste Nationale de Medicaments Essentiels’ AND Africa AND/OR < Name of African country > was conducted. The number of medicines on the national lists were compared according to a predefined template of medicines; and the percentage similarity calculated. Descriptive statistics were derived using STATA. Results Forty-seven countries in the WHO Africa region have developed a National Essential Medicines List. Eleven countries do not have any medicines listed for rheumatic diseases. The majority of countries had less than or equal to 50% similarity with the WHO EML for rheumatic disease in children and young people, median 3 medicines (IQR 1— 4). The most common medicines on the national lists from Africa were methotrexate, sulfasalazine and azathioprine, with etanercept available in 6 countries. Seven countries had only one medicine, acetylsalicylic acid listed in the section ‘Juvenile Joint diseases’. A multiple linear regression model for the predictors of the number of medicines on the national lists established that 20% of the variability was predicted by health expenditure per capita, socio-demographic index and the availability of rheumatology services (adult and/or paediatric) p  = 0.006, with socio-demographic index ( p  = 0.035, 95% CI 0.64—16.16) and the availability of rheumatology services ( p  = 0.033, 95% CI 0.13 – 2.90) significant. Conclusion Four countries (8.5%) in Africa have updated their National Essential Medicines Lists to reflect adequate care for children and young people with rheumatic diseases. Moving forward, efforts should focus on aligning available medicines with the WHO EML, and strengthening healthcare policy for rheumatology and pharmaceutical services, for affordable access to care and medicines.

Background Many children with rheumatic and musculoskeletal diseases are unrecognized. Identifying these children requires health care provider awareness, knowledge, and skills to recognize disease features and how (and when) to refer to specialist care. The aim of this paper is to highlight the need for better access to health care, review the essential role that education and virtual care play to address unmet need in low resource areas and especially to expand workforce capacity. Using collaborative partnerships, virtual platforms, and innovative assessment methods, musculoskeletal care and education can be delivered to reach a greater audience than ever before. Increased awareness through multiple initiatives and readily available resources are imperative to improve global rheumatology care. Conclusion The needs of children with rheumatic diseases and musculoskeletal conditions are vastly underserved around the world resulting in preventable morbidity and mortality. Expanded implementation of virtual education and e-health care platforms provides an opportunity to increase access to care for children globally.

Background Delay in diagnosis and access to specialist care is a major problem for many children and young people with rheumatic disease in sub-Saharan Africa. Most children with symptoms of rheumatic disease present to non-specialists for care. There is an urgent need to understand and scale-up paediatric rheumatology knowledge and skills amongst non-specialist healthcare workers to promote early diagnosis, prompt referral, and management. Purpose We evaluated the knowledge, attitudes and practices towards diagnosis and care of paediatric rheumatology patients among health care workers in Kenya. Methods We conducted 12 focus group discussions with clinical officers (third-tier community health workers) nurses, general practitioners and paediatricians across 6 regions in Kenya. Interviews were conducted on zoom, audio-recorded, transcribed, and analysed using NVIVO software. Results A total of 68 individuals participated; 11 clinical officers, 12 nurses, 10 general practitioners, 27 paediatricians and 7 others. Most ( n  = 53) were female, and the median age was 36 years (range 31–40 years). Fifty per cent of the participants (34 of 68) worked in public health facilities. Our study revealed gaps in knowledge of paediatric rheumatology amongst healthcare workers which contributes to delayed diagnosis and poor management. Healthcare workers reported both positive and negative attitudes towards diagnosis and care of paediatric rheumatology patients. Perceived complexity and lack of knowledge in diagnosis, management and lack of health system clinical pathways made all cadres of healthcare workers feel helpless, frustrated, inadequate and incompetent to manage paediatric rheumatology patients. Positive attitudes arose from a perceived feeling that paediatric rheumatology patients pose unique challenges and learning opportunities. Conclusion There is an urgent need to educate healthcare workers and improve health systems to optimize clinical care for paediatric rheumatology patients.

Background The PMM Portfolio is comprised of the Paediatric Musculoskeletal Matters (PMM) website, the paediatric Gait, Arms, Legs and Spine (pGALS) app and e-learning modules (ELM). The target audiences are non-specialists in paediatric musculoskeletal medicine. Our study aimed to evaluate impact on learning and clinical practice. Methods Mixed methods (analytics, online survey, interviews) were used with PMM and ELM registered users and purposive sampling of users using international contacts within paediatrics and paediatric rheumatology. Data was analysed using descriptive statistics and qualitative techniques. A Paired T-Test compared self-rated confidence before and after use of the PMM Portfolio. Results There has been wide reach for all the e-resources; PMM website (662,827 hits, 262,476 users, 214 countries, data 31st July 2020); pGALS app (12,670 downloads, 70 countries, data 31st July 2020); ELM (150 users, 30 countries, data 30th May 2019). There were 164 responses (students, trainees and health care professionals) to the survey from 25 countries. Most responders deemed the PMM Portfolio useful / very useful for their learning with significantly increased self-rated confidence in their clinical examination and reasoning skills following access to the PMM website, p  = < 0.01, pGALS app, p  = < 0.01 and ELM, p  = < 0.01. The most popular PMM website pages related to clinical assessment techniques (especially pGALS). There was high uptake of the pGALS app and pGALS ELM especially from trainees and allied health professionals. Many clinicians reported the PMM Portfolio to be useful when used to teach others. User feedback reported that easy navigation, open access, clinical images and cases were the most valued features. User feedback highlighted need to increase awareness of the e-resources through training programmes. Conclusions The PMM Portfolio was developed to aid learning for clinicians who are not specialists in paediatric MSK medicine. Our evaluation demonstrates wide international reach and positive feedback on learning. The PMM Portfolio is a highly useful e-resource for paediatric rheumatologists in their teaching of others to raise awareness, facilitate early diagnosis and referral of children with suspected disease. The wide user engagement informed future PMM Portfolio development and the mixed method of evaluation is transferable to other e-resources.

Background Many children and young people with juvenile idiopathic arthritis (JIA) experience delay in diagnosis and access to right care. The reasons for delay are multi-factorial and influenced by patient and family, clinician and organisational factors. Our aim was to explore the experiences of care, from initial symptoms to initial referral to paediatric rheumatology. Methods We analysed one-to-one and joint qualitative interviews with families of children with JIA (n = 36) presenting to a regional paediatric rheumatology service in the UK. We interviewed 51 family members (including mothers, fathers, patients, grandmothers and an aunt) and 10 health professionals (including orthopaedic surgeons, paediatricians, paediatric immunologist, General Practitioner and nurse) and a teacher involved in the care pathway of these JIA patients. Interviews were audio-recorded and analysed according to the standard procedures of rigorous qualitative analysis - coding, constant comparison, memoing and deviant case analysis. Results The median age of the children was 6 years old (range 1–17), with a spread of JIA subtypes. The median reported time to first PRh MDT visit from symptom onset was 22 weeks (range 4-364 weeks). Three key factors emerged in the pathways to appropriate care: (i) the persistence of symptoms (e.g. ‘change’ such as limp or avoidance of previously enjoyed activities) ; (ii) the persistence of parents help-seeking actions (e.g. repeat visits to primary and hospital care with concern that their child is not ‘normal’ ; iii) the experience and skills of health professionals resulting in different trajectories ( e.g. no-real-concern-at-this-point or further-investigation-is-required). JIA was more likely to be considered amongst health practitioner if they had prior experiences of a child with JIA (moreso with a ‘protracted pathway’) or exposure to paediatric rheumatology in their training. Conversely JIA was more likely to be overlooked if the child had c omorbidity such as learning disability or a chronic illness . Conclusions Care pathways are often ‘turbulent’ prior to a diagnosis of JIA with physical and emotional distress for families. There is need for greater awareness about JIA amongst health care professionals and observations of change (from family and non-health care professionals such as teachers) are key to trigger referral for paediatric rheumatology opinion.

Background Due to the paucity of paediatric rheumatologists in Kenya, it is paramount that we explore strategies to bridge clinical care gaps for paediatric rheumatology patients in order to promote early diagnosis, prompt referral, and optimal management. Purpose To identify proposed interventions which can improve the ability of non-specialist healthcare workers to care for paediatric rheumatology patients across Kenya. Methods We conducted 12 focus group discussions with clinical officers (community physician assistants), nurses, general practitioners and paediatricians across six regions in Kenya. Interviews were conducted, audio-recorded, transcribed verbatim, and analysed using MAXQDA 2022.2 software. Results A total of 68 individuals participated in the study; 11 clinical officers, 12 nurses, 10 general practitioners, 27 paediatricians and eight other healthcare workers. Proposed patient interventions included patient education and psychosocial support. Community interventions were outreach awareness campaigns, mobilising financial support for patients’ care, mobilising patients to access diagnostic and therapeutic interventions. Healthcare worker interventions include diagnostic, management, and referral guidelines, as well as research and educational interventions related to symptom identification, therapeutic strategies, and effective patient communication skills. In addition, it was highlighted that healthcare systems should be bolstered to improve insurance coverage and access to integrated multi-disciplinary clinical care. Conclusions Study participants were able to identify potential initiatives to improve paediatric rheumatology care in Kenya. Additional efforts are underway to design, implement and monitor the impact of some of these potential interventions,

Background The use of telemedicine in pediatric rheumatology has been historically low. The current COVID 19 global pandemic has forced a paradigm shift with many centers rapidly adopting virtual visits to conduct care resulting in rapid expansion of use of telemedicine amongst practices. Body This commentary discusses practical tips for physicians including guidance around administrative and governance issues, preparation for telemedicine, involving the multidisciplinary care team, and teaching considerations. We also outline a standard proforma and smart phrases for the electronic health record. A proposed variation of the validated pediatric gait arms legs spine examination (pGALS) called the video pGALS (VpGALS) as a means of conducting virtual pediatric rheumatology physical examination is presented. Conclusion This commentary provides a starting framework for telemedicine use in pediatric rheumatology and further work on validation and acceptability is needed.

Juvenile idiopathic arthritis (JIA) is the most prevalent chronic rheumatic disease in children and young people (CYP) and a major cause of pain and disability. The vast majority of the world’s children and their families live in less resourced countries (LRCs) and face significant socioeconomic and healthcare challenges. Current recommendations for standards of care and treatment for children with JIA do not consider children living in less resourced countries. In order to develop appropriate recommendations for the care of CYP with JIA in less resourced countries a meeting of experienced pediatric rheumatologists from less resourced countries was convened with additional input from a steering group of international pediatric rheumatologists with experience in developing recommendations and standards of care for JIA. Following a needs assessment survey of healthcare workers caring for CYP with JIA in LRC, a literature review was carried out and management recommendations formulated using Delphi technique and a final consensus conference. Responses from the needs assessment were received from 121/483 (25%) practitioners from 25/49 (51%) less resourced countries. From these responses, the initial 84 recommendations were refined and expanded through a series of 3 online Delphi rounds. A final list of 90 recommendations was proposed for evaluation. Evidence for each statement was reviewed, graded, and presented to the consensus group. The degree of consensus, level of agreement, and level of evidence for these recommendations are reported. Recommendations arrived at by consensus for CYP with JIA in less resourced countries cover 5 themes: (1) diagnosis, (2) referral and monitoring, (3) education and training, (4) advocacy and networks, and (5) research. Thirty-five statements were drafted. All but one statement achieved 100% consensus. The body of published evidence was small and the quality of evidence available for critical appraisal was low. Our recommendations offer novel insights and present consensus-based strategies for the management of JIA in less resourced countries. The emphasis on communicable and endemic diseases influencing the diagnosis and treatment of JIA serves as a valuable addition to existing JIA guidelines. With increasing globalization, these recommendations as a whole provide educational and clinical utility for clinicians worldwide. The low evidence base for our recommendations reflects a shortage of research specific to less resourced countries and serves as an impetus for further inquiry towards optimizing care for children with JIA around the world.