Three- and five-year outcomes of an inception cohort of Australian children with juvenile idiopathic arthritis.

BACKGROUND: To describe the 3- and 5-year outcomes of an inception cohort of Australian children with JIA for whom 1-year outcomes have previously been published. METHODS: Data regarding clinical outcomes of the original cohort of 134 patients at 3 and 5 years were sought. Relevant clinical features and medication exposures entered prospectively into an electronic record were collected and analyzed using descriptive statistics. RESULTS: Data were available for 110 and 98 patients at 3 and 5 years, respectively. The proportion of patients with active joints progressively decreased from 34% at 12 months to 21% at 3 years and 16% at 5 years. Cumulative exposure to methotrexate increased between 3 and 5 years (75%-80%), however, point prevalence use decreased (45%-41%). Cumulative exposure and point prevalence use of bDMARDS both increased between 3 and 5 years; 30%-42% and 29%-33%, respectively. Thirty-five percent of patients had inactive joint disease off medications at 5 years, which occurred most frequently in patients with sJIA and oligoarthritis. CONCLUSION: Five-year outcomes of Australian children with JIA are good, with only a small minority having ongoing active joint disease at 5 years. bDMARDS play an increasing role in management over time; however, methotrexate use remains significant. A majority of children remain on medications at 5 years.

Methotrexate for juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. Methotrexate has broad immunomodulatory properties and is the most commonly used disease-modifying antirheumatic drug (DMARD). This is an update of a 2001 Cochrane review. It supports a living guideline for children and young people with JIA. OBJECTIVES: To assess the benefits and harms of methotrexate for children and young people with juvenile idiopathic arthritis. SEARCH METHODS: The Australian JIA Living Guideline Working Group created a registry of all randomised controlled trials (RCTs) of JIA by searching CENTRAL, MEDLINE, Embase, and trials registries. The date of the most recent search of online databases was 1 February 2023. SELECTION CRITERIA: We searched for RCTs that compared methotrexate with placebo, no treatment, or another DMARD (with or without concomitant therapies) in children and young people (aged up to 18 years) with JIA. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. The main comparison was methotrexate versus placebo. Our outcomes were treatment response, sustained clinically inactive disease, function, pain, participant global assessment of well-being, serious adverse events, and withdrawals due to adverse events. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified three new trials in this update, bringing the total number of included RCTs to five (575 participants). Three trials evaluated oral methotrexate versus placebo, one evaluated methotrexate plus intra-articular glucocorticoid (IAGC) therapy versus IAGC therapy alone, and one evaluated methotrexate versus leflunomide. Doses of methotrexate ranged from 5 mg/m2/week to 15 mg/m2/week in four trials, and participants in the methotrexate group of the remaining trial received 0.5 mg/kg/week. Trial size varied from 31 to 226 participants. The average age of participants ranged from four to 10 years. Most participants were females and most had nonsystemic JIA. The study that evaluated methotrexate plus IAGC therapy versus IAGC therapy alone recruited children and young people with the oligoarticular disease subtype of JIA. Two placebo-controlled trials and the trial of methotrexate versus leflunomide were adequately randomised and blinded, and likely not susceptible to important biases. One placebo-controlled trial may have been susceptible to selection bias due to lack of adequate reporting of randomisation methods. The trial investigating the addition of methotrexate to IAGC therapy was susceptible to performance and detection biases. Methotrexate versus placebo Methotrexate compared with placebo may increase the number of children and young people who achieve treatment response up to six months (absolute difference of 163 more per 1000 people; risk ratio (RR) 1.67, 95% confidence interval (CI) 1.21 to 2.31; I2 = 0%; 3 trials, 328 participants; low-certainty evidence). However, methotrexate compared with placebo may have little or no effect on pain as measured on an increasing scale of 0 to 100 (mean difference (MD) -1.10 points, 95% CI -9.09 to 6.88; 1 trial, 114 participants), improvement in participant global assessment of well-being (absolute difference of 92 more per 1000 people; RR 1.23, 95% CI 0.88 to 1.72; 1 trial, 176 participants), occurrence of serious adverse events (absolute difference of 5 fewer per 1000 people; RR 0.63, 95% CI 0.04 to 8.97; 3 trials, 328 participants), and withdrawals due to adverse events (RR 3.46, 95% CI 0.60 to 19.79; 3 trials, 328 participants) up to six months. We could not estimate the absolute difference for withdrawals due to adverse events because there were no withdrawals in the placebo group. All outcomes were reported within six months of randomisation. We downgraded the certainty of the evidence to low for all outcomes due to indirectness (suboptimal dosing of methotrexate and diverse outcome measures) and imprecision (few participants and low event rates). No trials reported function or the number of participants with sustained clinically inactive disease. Serious adverse events included liver derangement, abdominal pain, and inadvertent overdose. Methotrexate plus intra-articular corticosteroid therapy versus intra-articular corticosteroid therapy alone Methotrexate plus IAGC therapy compared with IAGC therapy alone may have little or no effect on the probability of sustained clinically inactive disease or the rate of withdrawals due to adverse events up to 12 months in children and young people with the oligoarticular subtype of JIA (low-certainty evidence). We could not calculate the absolute difference in withdrawals due to adverse events because there were no withdrawals in the control group. We are uncertain if there is any difference between the interventions in the risk of severe adverse events, because none were reported. The study did not report treatment response, function, pain, or participant global assessment of well-being. Methotrexate versus an alternative disease-modifying antirheumatic drug Methotrexate compared with leflunomide may have little or no effect on the probability of treatment response or on function, participant global assessment of well-being, risk of serious adverse events, and rate of withdrawals due to adverse events up to four months. We downgraded the certainty of the evidence for all outcomes to low due to imprecision. The study did not report pain or sustained clinically inactive disease. AUTHORS' CONCLUSIONS: Oral methotrexate (5 mg/m2/week to 15 mg/m2/week) compared with placebo may increase the number of children and young people achieving treatment response but may have little or no effect on pain or participant global assessment of well-being. Oral methotrexate plus IAGC injections compared to IAGC injections alone may have little or no effect on the likelihood of sustained clinically inactive disease among children and young people with oligoarticular JIA. Similarly, methotrexate compared with leflunomide may have little or no effect on treatment response, function, and participant global assessment of well-being. Serious adverse events due to methotrexate appear to be rare. We will update this review as new evidence becomes available to inform the living guideline.

Defining patient perception of overall well-being and disease activity in the OMERACT Juvenile Idiopathic Arthritis (JIA) core domain set: A report from the JIA working group.

OBJECTIVE: The OMERACT Juvenile Idiopathic Arthritis (JIA) Working Group (WG) aimed to reach agreement on a consensus-based definition and description of the core domain related to patient perception of overall well-being and disease activity. METHODS: A committee of patient research partners, clinicians, methodologists, and researchers drafted working definitions and descriptions. The WG conducted two iterative electronic stakeholder surveys to obtain consensus on domain description, definition, and the distinction between patient perception of overall well-being and disease activity. These definitions were then presented at the OMERACT 2023 Special Interest Group (SIG) session for agreement. RESULTS: Forty-five participants, from 7 countries and 4 continents, were comprised of six patients, 18 caregivers, and 21 healthcare providers. The consensus threshold (70%) was exceeded on all survey questions from both stakeholder groups (patients/caregivers, all others). Agreement was obtained on the new definition, description, and domain title, along with agreement on separate assessments of two target domains, patient perception of overall well-being as it relates to disease and patient perception of disease activity. CONCLUSION: Through an iterative consensus process and achieving agreement from the OMERACT SIG session attendees, the JIA WG has created a detailed definition and description for the two target domains in the patient perception of overall well-being related to disease core domain of the JIA mandatory core domain set. The next phase of this work will be instrument selection using the OMERACT filter 2.2.

Patterns and rates of confirmed transfer of care of patients with juvenile idiopathic arthritis at a tertiary paediatric rheumatology centre.

BACKGROUND: Disease activity in juvenile idiopathic arthritis (JIA) commonly persists into adulthood. Transfer of JIA patients to adult healthcare services can be challenging, with prior studies showing poor rates of success. AIMS: This audit sought to examine characteristics of patients undergoing transfer of care within the rheumatology unit at the Royal Children's Hospital in Melbourne, with the aim of identifying areas for improvement. Specifically, we sought to determine the rate at which confirmation of established care with an adult service (confirmed transfer of care) was documented in the patient chart. METHODS: Patients with a diagnosis of JIA who turned 18 years of age between 2012 and 2019 were identified. A chart review was undertaken to collect relevant data. RESULTS: One hundred and seventy-seven patients were identified. In all, 64% (114/177) were referred for adult care. The commonest JIA subtypes referred were seronegative polyarticular (35/114; 30.7%) and oligoarticular JIA (22/114; 19.3%). Documentation of confirmed transfer of care occurred in 62.3% (71/114), with correspondence received from adult services in 49.1% (56/114). There was no difference in rate of return correspondence from public versus private providers (45% vs 53.8%; P = 0.38). The use of 'backstop appointments' was more likely in those with confirmed transfer of care (66% vs 30%; P = 0.0002). CONCLUSIONS: Lack of confirmed transfer of care for JIA patients is common and carries a risk of suboptimal outcomes. Strategies to improve communication with adult services, the routine use of 'backstop' appointments and vigilance regarding potential loss to follow up at the time of transfer would minimise this risk.

Factors impacting COVID-19 vaccine decision making in older adults and people with underlying conditions in Victoria, Australia: A cross-sectional survey.

Australia's COVID-19 vaccine rollout included prioritizing older adults and those with underlying conditions. However, little was known around the factors impacting their decision to accept the vaccine. This study aimed to assess vaccine intentions, information needs, and preferences of people prioritized to receive the COVID-19 vaccine at the start of the Australian vaccine rollout. A cross-sectional online survey of people aged ≥70 years or 18-69 with chronic or underlying conditions was conducted between 12 February and 26 March 2021 in Victoria, Australia. The World Health Organization Behavioural and Social Drivers of COVID-19 vaccination framework and items informed the survey design and framing of results. Bivariate logistic regression was used to investigate the association between intention to accept a COVID-19 vaccine and demographic characteristics. In total, 1828 eligible people completed the survey. Intention to vaccinate was highest among those ≥70 years (89.6%, n = 824/920) versus those aged 18-69 years (83.8%, n = 761/908), with 91% (n = 1641/1803) of respondents agreeing that getting a COVID-19 vaccine was important to their health. Reported vaccine safety (aOR 1.4, 95% CI 1.1 to 1.8) and efficacy (aOR 1.9, 95% CI 1.5 to 2.3) were associated with intention to accept a COVID-19 vaccine. Concerns around serious illness, long-term effects, and insufficient vaccine testing were factors for not accepting a COVID-19 vaccine. Preferred communication methods included discussion with healthcare providers, with primary care providers identified as the most trusted information source. This study identified factors influencing the prioritized public's COVID-19 vaccine decision-making, including information preferences. These details can support future vaccination rollouts.

Modified Delphi study to identify priority clinical questions for the Australian living guidelines for the management of Juvenile Idiopathic Arthritis.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is the most common rheumatic inflammatory disease in childhood. Optimal management requires clinicians to be up to date with the rapidly evolving evidence base. 'Living' evidence-based clinical practice guidelines, which integrate new evidence as soon as it is available, are a novel method to enhance the translation of research into practice. To determine the most relevant questions that should be prioritised in national Australian JIA living guidelines, we invited Australian and New Zealand paediatric rheumatologists and other relevant health professionals to identify and rank their most important questions in order of priority. METHODS: All 47 members of the Australian Paediatric Rheumatology Group (APRG) were invited to participate in a modified Delphi study comprising two rounds. The first round identified demographic information of respondents, current attitudes to guideline use and invited submission of priority management questions. The second round asked respondents to rank 27 collated and refined questions identified in round one in order of priority. RESULTS: There were 29 (62%) and 28 (60%) responses to the first and second survey rounds respectively. About two thirds were rheumatologists or trainees (66, 68%), nearly half had more than 10 years of experience (45, 46%) and practice setting was largely hospital (79, 86%) and urban (86, 75%). Most respondents used clinical guidelines in their practice (72% sometimes, 24% often), most frequently American College of Rheumatology (ACR) (66%) and European Alliance of Associations for Rheumatology (EULAR) (59%) guidelines. Reported barriers to guideline use included that they are not up to date and access difficulties. Most respondents (83%) considered Australian guidelines were necessary and two-thirds indicated they would use them if integrated into practice software. The highest ranked topics were down-titration and discontinuation of disease modifying anti-rheumatic drugs (ranked first), best outcome measures (second) and treatment targets in JIA (third). CONCLUSIONS: There is strong clinician support for the development of Australian living guidelines for JIA. Consensus was reached on the ten top-ranked priority questions. Our guidelines will develop evidence-based recommendations for these high priority questions that will be updated in real time as needed to facilitate rapid translation of evidence into clinical practice.

Identification of Novel Loci Shared by Juvenile Idiopathic Arthritis Subtypes Through Integrative Genetic Analysis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common chronic immune-mediated joint disease among children and encompasses a heterogeneous group of immune-mediated joint disorders classified into 7 subtypes according to clinical presentation. However, phenotype overlap and biologic evidence suggest a shared mechanistic basis between subtypes. This study was undertaken to systematically investigate shared genetic underpinnings of JIA subtypes. METHODS: We performed a heterogeneity-sensitive genome-wide association study encompassing a total of 1,245 JIA cases (classified into 7 subtypes) and 9,250 controls, followed by fine-mapping of candidate causal variants at each genome-wide significant locus, functional annotation, and pathway and network analysis. We further identified candidate drug targets and drug repurposing opportunities by in silico analyses. RESULTS: In addition to the major histocompatibility complex locus, we identified 15 genome-wide significant loci shared between at least 2 JIA subtypes, including 10 novel loci. Functional annotation indicated that candidate genes at these loci were expressed in diverse immune cell types. CONCLUSION: This study identified novel genetic loci shared by JIA subtypes. Our findings identified candidate mechanisms underlying JIA subtypes and candidate targets with drug repurposing opportunities for JIA treatment.

Qualitative exploration of intentions, concerns and information needs of vaccine-hesitant adults initially prioritised to receive COVID-19 vaccines in Australia.

OBJECTIVE: Tailored communication is necessary to address COVID-19 vaccine hesitancy and increase uptake. We aimed to understand the information needs, perceived benefits and barriers to COVID-19 vaccination of people prioritised, but hesitant to receive the vaccine. METHOD: In this qualitative study in Victoria, Australia (February-May 2021), we purposively sampled hesitant adults who were health or aged/disability care workers (n=20), or adults aged 18-69 with comorbidities or aged ≥70 years ('prioritised adults'; n=19). We thematically analysed interviews inductively, then deductively organised themes within the World Health Organization Behavioural and Social Drivers of vaccination model. Two stakeholder workshops (n=12) explored understanding and preferences for communicating risks and benefits. We subsequently formed communication recommendations. RESULTS: Prioritised adults and health and aged care workers had short- and long-term safety concerns specific to personal circumstances, and felt like "guinea pigs". They saw vaccination as beneficial for individual and community protection and travel. Some health and aged care workers felt insufficiently informed to recommend vaccines, or viewed this as outside their scope of practice. Workshop participants requested interactive materials and transparency from spokespeople about uncertainty. Conclusions and public health implications: Eleven recommendations address communication content, delivery and context to increase uptake and acceptance of COVID-19 vaccines.

High levels of psychosocial distress among Australian frontline healthcare workers during the COVID-19 pandemic: a cross-sectional survey.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a profound and prolonged impact on healthcare services and healthcare workers. AIMS: The Australian COVID-19 Frontline Healthcare Workers Study aimed to investigate the severity and prevalence of mental health issues, as well as the social, workplace and financial disruptions experienced by Australian healthcare workers during the COVID-19 pandemic. METHODS: A nationwide, voluntary, anonymous, single timepoint, online survey was conducted between 27 August and 23 October 2020. Individuals self-identifying as frontline healthcare workers in secondary or primary care were invited to participate. Participants were recruited through health organisations, professional associations or colleges, universities, government contacts and national media. Demographics, home and work situation, health and psychological well-being data were collected. RESULTS: A total of 9518 survey responses were received; of the 9518 participants, 7846 (82.4%) participants reported complete data. With regard to age, 4110 (52.4%) participants were younger than 40 years; 6344 (80.9%) participants were women. Participants were nurses (n=3088, 39.4%), doctors (n=2436, 31.1%), allied health staff (n=1314, 16.7%) or in other roles (n=523, 6.7%). In addition, 1250 (15.9%) participants worked in primary care. Objectively measured mental health symptoms were common: mild to severe anxiety (n=4694, 59.8%), moderate to severe burnout (n=5458, 70.9%) and mild to severe depression (n=4495, 57.3%). Participants were highly resilient (mean (SD)=3.2 (0.66)). Predictors for worse outcomes on all scales included female gender; younger age; pre-existing psychiatric condition; experiencing relationship problems; nursing, allied health or other roles; frontline area; being worried about being blamed by colleagues and working with patients with COVID-19. CONCLUSIONS: The COVID-19 pandemic is associated with significant mental health symptoms in frontline healthcare workers. Crisis preparedness together with policies and practices addressing psychological well-being are needed.

Coping strategies adopted by Australian frontline health workers to address psychological distress during the COVID-19 pandemic.

OBJECTIVES: The Australian COVID-19 Frontline Healthcare Workers Study investigated coping strategies and help-seeking behaviours, and their relationship to mental health symptoms experienced by Australian healthcare workers (HCWs) during the COVID-19 pandemic. METHODS: Australian HCWs were invited to participate a nationwide, voluntary, anonymous, single time-point, online survey between 27th August and 23rd October 2020. Complete responses on demographics, home and work situation, and measures of health and psychological wellbeing were received from 7846 participants. RESULTS: The most commonly reported adaptive coping strategies were maintaining exercise (44.9%) and social connections (31.7%). Over a quarter of HCWs (26.3%) reported increased alcohol use which was associated with a history of poor mental health and worse personal relationships. Few used psychological wellbeing apps or sought professional help; those who did were more likely to be suffering from moderate to severe symptoms of mental illness. People living in Victoria, in regional areas, and those with children at home were significantly less likely to report adaptive coping strategies. CONCLUSIONS: Personal, social, and workplace predictors of coping strategies and help-seeking behaviour during the pandemic were identified. Use of maladaptive coping strategies and low rates of professional help-seeking indicate an urgent need to understand the effectiveness of, and the barriers and enablers of accessing, different coping strategies.

The Effect of UK Nursing Policy on Higher Education Wound Care Provision and Practice: A Critical Discourse Analysis.

In the United Kingdom, significant ongoing inconsistency exists in wound care nursing education provision and practice. Health economists have identified this to be a major cause of the burgeoning economic and personal cost of successfully, and equitably, healing chronic wounds. While numerous wound care educational resources exist, policies intended to implement a program of reform or change are for some reason not filtering down to, or being implemented by, those who need them most. Policy making processes do not appear to be operating as efficiently as they should, and this merits further scrutiny. A critical discourse analysis of two UK professional body wound care policies provided an innovative insight into the effect of policy production to the research problem. The overarching construct of "Aspiration and Resolution" and its subconstructs were identified. Links between data, analysis, and conclusions were established using Greckhamer and Cilesiz's (2014) framework to address criticisms over lack of transparency in critical discourse analysis methodology. Findings indicate wound care policy makers must adopt an active, not passive, approach to policy making. An active position, compared with the inertia that appears to currently exist, would take into consideration the capacity to implement policy and not merely increase awareness or disseminate. Wound healing policy making agencies need to make decisions on how to disseminate and implement policy. Active policy making would also adopt target audiences' decisions to implement policy, instigate activities to improve knowledge and skills, facilitate change, and ensure continued use of policy as part of organizational operations.

Factors Influencing Australian Healthcare Workers' COVID-19 Vaccine Intentions across Settings: A Cross-Sectional Survey.

Healthcare workers' COVID-19 vaccination coverage is important for staff and patient safety, workforce capacity and patient uptake. We aimed to identify COVID-19 vaccine intentions, factors associated with uptake and information needs for healthcare workers in Victoria, Australia. We administered a cross-sectional online survey to healthcare workers in hospitals, primary care and aged or disability care settings (12 February-26 March 2021). The World Health Organization Behavioural and Social Drivers of COVID-19 vaccination framework informed survey design and framing of results. Binary regression results adjusted for demographics provide risk differences between those intending and not intending to accept a COVID-19 vaccine. In total, 3074 healthcare workers completed the survey. Primary care healthcare workers reported the highest intention to accept a COVID-19 vaccine (84%, 755/898), followed by hospital-based (77%, 1396/1811) and aged care workers (67%, 243/365). A higher proportion of aged care workers were concerned about passing COVID-19 to their patients compared to those working in primary care or hospitals. Only 25% felt they had sufficient information across five vaccine topics, but those with sufficient information had higher vaccine intentions. Approximately half thought vaccines should be mandated. Despite current high vaccine rates, our results remain relevant for booster programs and future vaccination rollouts.

Genomic risk scores for juvenile idiopathic arthritis and its subtypes.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is an autoimmune disease and a common cause of chronic disability in children. Diagnosis of JIA is based purely on clinical symptoms, which can be variable, leading to diagnosis and treatment delays. Despite JIA having substantial heritability, the construction of genomic risk scores (GRSs) to aid or expedite diagnosis has not been assessed. Here, we generate GRSs for JIA and its subtypes and evaluate their performance. METHODS: We examined three case/control cohorts (UK, US-based and Australia) with genome-wide single nucleotide polymorphism (SNP) genotypes. We trained GRSs for JIA and its subtypes using lasso-penalised linear models in cross-validation on the UK cohort, and externally tested it in the other cohorts. RESULTS: The JIA GRS alone achieved cross-validated area under the receiver operating characteristic curve (AUC)=0.670 in the UK cohort and externally-validated AUCs of 0.657 and 0.671 in the US-based and Australian cohorts, respectively. In logistic regression of case/control status, the corresponding odds ratios (ORs) per standard deviation (SD) of GRS were 1.831 (1.685 to 1.991) and 2.008 (1.731 to 2.345), and were unattenuated by adjustment for sex or the top 10 genetic principal components. Extending our analysis to JIA subtypes revealed that the enthesitis-related JIA had both the longest time-to-referral and the subtype GRS with the strongest predictive capacity overall across data sets: AUCs 0.82 in UK; 0.84 in Australian; and 0.70 in US-based. The particularly common oligoarthritis JIA also had a GRS that outperformed those for JIA overall, with AUCs of 0.72, 0.74 and 0.77, respectively. CONCLUSIONS: A GRS for JIA has potential to augment clinical JIA diagnosis protocols, prioritising higher-risk individuals for follow-up and treatment. Consistent with JIA heterogeneity, subtype-specific GRSs showed particularly high performance for enthesitis-related and oligoarthritis JIA.

Challenges in the diagnosis and treatment of disabling pansclerotic morphea of childhood: case-based review.

Disabling pansclerotic morphea of childhood (DPMC) is a rare subtype of juvenile localized scleroderma (JLS) characterized by pansclerosis mainly affecting children under the age of 14. This aggressive disease has a poor prognosis due to the rapid progression of deep musculoskeletal atrophy resulting in cutaneous ulceration and severe joint contractures. We describe the challenges in treating a previously well 5-year-old male who has refractory symptoms of DPMC. Over the 29 months, since his initial presentation, we trialed over ten therapies. There was subjective improvement with prednisolone and mycophenolate mofetil (MMF). However, other therapies including biologics and tyrosine kinase inhibitors (TKI) were ineffective. The patient has been referred for hematopoietic stem cell transplant given ongoing disease progression. We conducted a literature search focusing on English articles with keywords including DPMC. Publications with limited information or describing cases aged 20 and above were excluded. Thirty-seven case reports were identified and the reported treatments were evaluated. Methotrexate and corticosteroids have been the most commonly utilized. MMF has been anecdotally effective. Biologics, TKI, and Janus kinase inhibitors lack evidence in DPMC, but have had demonstrated efficacy in similar pathologies including systemic sclerosis, and, thus, have been used for DPMC. Phototherapy has been documented to be reducing skin thickness and stiffness of plaques. Eventually, most children require multi-modal and high-dose immunosuppressive therapies to reduce the inflammation inflicted by the disease. Long-term antibiotics and nutritional support are important in the ongoing care of these patients.

Establishing an Updated Core Domain Set for Studies in Juvenile Idiopathic Arthritis: A Report from the OMERACT 2018 JIA Workshop.

OBJECTIVE: The current Juvenile Idiopathic Arthritis (JIA) Core Set used in randomized controlled trials (RCT) and longitudinal observational studies (LOS) was developed without the input of patients/parents. At the Outcome Measures in Rheumatology (OMERACT) 2016, a special interest group voted to reconsider the core set, incorporating broader input. We describe subsequent work culminating in an OMERACT 2018 plenary and consensus voting. METHODS: Candidate domains were identified through literature review, qualitative surveys, and online discussion boards (ODB) held with patients with JIA and parents in Australia, Italy, and the United States. A Delphi process with parents, patients, healthcare providers, researchers, and regulators served to edit the domain list and prioritize candidate domains. After the presentation of results, OMERACT workshop participants voted, with consensus set at > 70%. RESULTS: Participants in ODB were 53 patients with JIA (ages 15-24 yrs) and 55 parents. Three rounds of Delphi considering 27 domains were completed by 190 (response rate 85%), 201 (84%), and 182 (77%) people, respectively, from 50 countries. There was discordance noted between domains prioritized by patients/parents compared to others. OMERACT conference voting approved domains for JIA RCT and LOS with 83% endorsement. Mandatory domains are pain, joint inflammatory signs, activity limitation/physical function, patient's perception of disease activity (overall well-being), and adverse events. Mandatory in specific circumstances: inflammation/other features relevant to specific JIA categories. CONCLUSION: Following the OMERACT methodology, we developed an updated JIA Core Domain Set. Next steps are to identify and systematically evaluate best outcome measures for these domains.

Association of Increased Sun Exposure Over the Life-course with a Reduced Risk of Juvenile Idiopathic Arthritis.

Cutaneous sun exposure is an important determinant of circulating vitamin D. Both sun exposure and vitamin D have been inversely associated with risk of autoimmune disease. In juvenile idiopathic arthritis (JIA), low circulating vitamin D appears common, but disease-related behavioral changes may have influenced sun exposure. We therefore aimed to determine whether predisease sun exposure is associated with JIA. Using validated questionnaires, we retrospectively measured sun exposure for 202 Caucasian JIA case-control pairs born in Victoria Australia, matched for birth year and time of recruitment. Measures included maternal sun exposure at 12 weeks of pregnancy and child sun exposure across the life-course prediagnosis. We converted exposure to UVR dose and looked for case-control differences using logistic regression, adjusting for potential confounders. Higher cumulative prediagnosis UVR exposure was associated with reduced risk of JIA, with a clear dose-response relationship (trend P = 0.04). UVR exposure at 12 weeks of pregnancy was similarly inversely associated with JIA (trend P = 0.011). Associations were robust to sensitivity analyses for prediagnosis behavioral changes, disease duration and knowledge of the hypothesis. Our data indicate that lower UVR exposure may increase JIA risk. This may be through decreased circulating vitamin D, but prospective studies are required to confirm this.

Juvenile idiopathic arthritis managed in the new millennium: one year outcomes of an inception cohort of Australian children.

BACKGROUND: The advent of new treatments for Juvenile Idiopathic Arthritis (JIA) has prompted interest in systematically studying the outcomes of patients treated in the 'modern era'. Such data provide both benchmarks for assessing local outcomes and important information for use in counselling families of newly diagnosed patients. While data are available for cohorts in Europe and North America, no such data exist for Australian patients. The aim was to examine the demographics, treatment and outcomes at 12 months of an inception cohort of newly diagnosed patients with JIA at a single tertiary referral paediatric rheumatology centre in Australia. METHODS: Retrospective review of prospectively collected data from patients newly diagnosed with JIA between 2010 and 2014 at the Royal Children's Hospital in Melbourne. RESULTS: One hundred thirty four patients were included (62% female). Oligoarthritis was the single largest category of JIA (36%) and rheumatoid factor positive polyarthritis the least common (2%). Undifferentiated JIA accounted for 13% of patients and was the third largest category. Across the cohort 94% received NSAIDs, 53% oral steroids, 62% methotrexate and 15% a biologic DMARD. Intra-articular steroids were used in 62%, most commonly in the oligoarticular subtype (94%). 95% of patients achieved a joint count of zero at a median of 4.1 months, however flares occurred in 42%. At 12 months 65% had no active joint disease, though more than half remained on medication. CONCLUSION: Australian children with JIA managed in the modern era have similar characteristics and achieve short term outcomes comparable to cohorts in Europe and North America, with high rates of joint remission in the first 12 months of follow-up but with a significant relapse rate and requirement for ongoing medication.

Variations in bariatric surgical care pathways: a national costing study on the variability of services and impact on costs.

BACKGROUND: We undertook a survey of all bariatric centres in Scotland in order to describe current pre- and post-operative care, to estimate their costs and explore differences in financial impact. METHODS: A questionnaire was distributed to each health centre. Descriptive statistics were used to present average cost per patient along with 95% confidence intervals, and the range of costs. RESULTS: Results show nearly a five-fold difference in costs per patient for pre-operative services (range £226 - £1071) and more than a three-fold difference for post-operative services (range £259 - £896). CONCLUSIONS: There is a lack of evidence base and a clear requirement for the evaluation of bariatric surgical services to identify the care pathways pre- and post-surgery which lead to largest improvements in health outcomes and remain cost-effective.

The DNA methylation landscape of CD4+ T cells in oligoarticular juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is presumed to be driven by an adverse combination of genes and environment. Epigenetic processes, including DNA methylation, act as a conduit through which the environment can regulate gene activity. Altered DNA methylation has been associated with adult autoimmune rheumatic diseases such as rheumatoid arthritis, but studies are lacking for paediatric autoimmune rheumatic diseases including JIA. Here, we performed a genome-scale case-control analysis of CD4+ T cell DNA methylation from 56 oligoarticular JIA (oJIA) cases and 57 age and sex matched controls using Illumina HumanMethylation450 arrays. DNA methylation at each array probe was tested for association with oJIA using RUV (Remove Unwanted Variation) together with a moderated t-test. Further to this 'all-inclusive' analysis, we stratified by age at diagnosis (≤6yrs, >6yrs) and by sex as potential sources of heterogeneity. Following False Discovery Rate (FDR) adjustment, no probes were associated with oJIA in the all-inclusive, >6yrs-diagnosed, or sex-stratified analyses, and only one probe was associated with oJIA in the ≤6yrs-diagnosed analysis. We attempted technical validation and replication of 14 probes (punadj<0.01) at genes of known/potential relevance to disease. At VPS53, we demonstrated a regional shift towards higher methylation in oJIA (all-inclusive) compared to controls. At REEP3, where polymorphism has been previously associated with JIA, we demonstrated higher DNA methylation in male oJIA compared to male controls. This is the most comprehensive JIA case-control analysis of DNA methylation to date. While we have generated some evidence of altered methylation in oJIA, substantial differences are not apparent in CD4+ T cells. This may indicate a lesser relevance of DNA methylation levels in childhood, compared to adult, rheumatic disease.

Evidence for Updating the Core Domain Set of Outcome Measures for Juvenile Idiopathic Arthritis: Report from a Special Interest Group at OMERACT 2016.

OBJECTIVE: The current Juvenile Idiopathic Arthritis (JIA) Core Set was developed in 1997 to identify the outcome measures to be used in JIA clinical trials using statistical and consensus-based techniques, but without patient involvement. The importance of patient/parent input into the research process has increasingly been recognized over the years. An Outcome Measures in Rheumatology (OMERACT) JIA Core Set Working Group was formed to determine whether the outcome domains of the current core set are relevant to those involved or whether the core set domains should be revised. METHODS: Twenty-four people from the United States, Canada, Australia, and Europe, including patient partners, formed the working group. Guided by the OMERACT Filter 2.0 process, we performed (1) a systematic literature review of outcome domains, (2) a Web-based survey (142 patients, 343 parents), (3) an idea-generation study (120 parents), (4) 4 online discussion boards (24 patients, 20 parents), and (5) a Special Interest Group (SIG) activity at the OMERACT 13 (2016) meeting. RESULTS: A MEDLINE search of outcome domains used in studies of JIA yielded 5956 citations, of which 729 citations underwent full-text review, and identified additional domains to those included in the current JIA Core Set. Qualitative studies on the effect of JIA identified multiple additional domains, including pain and participation. Twenty-one participants in the SIG achieved consensus on the need to revise the entire JIA Core Set. CONCLUSION: The results of qualitative studies and literature review support the need to expand the JIA Core Set, considering, among other things, additional patient/parent-centered outcomes, clinical data, and imaging data.