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Objective: To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing 2005-2010 and 2017-2021 inception cohorts., Methods: Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan-Meier survival analysis and multivariable Cox regression., Results: The 2005-2010 and 2017-2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005-2010 and 26% (23, 30) in the 2017-2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for good health-related quality of life (≥9/10)., Conclusion: Although baseline disease characteristics were comparable in the 2005-2010 and 2017-2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient-reported outcomes were smaller than improvements in disease activity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The clinical decision-making process in paediatric arthritis lacks an objective, reliable bedside imaging tool. The aim of this study was to develop a US scanning protocol and assess the reliability of B-mode and Doppler scoring systems for inflammatory lesions of the paediatric ankle., Methods: As part of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) US group, 19 paediatric rheumatologists through a comprehensive literature review developed a set of standardized views and scoring systems to assess inflammatory lesions of the synovial recesses as well as tendons of the paediatric ankle. Three rounds of scoring of still images were followed by one practical exercise. Agreement among raters was assessed using two-way single score intraclass correlation coefficients (ICC)., Results: Of the 37 initially identified views to assess the presence of ankle synovitis and tenosynovitis, nine views were chosen for each B-mode and Doppler mode semi-quantitative evaluation. Several scoring exercises and iterative modifications resulted in a final highly reliable scoring system: anterior tibiotalar joint ICC: 0.93 (95% CI 0.92, 0.94), talonavicular joint ICC: 0.86 (95% CI 0.81, 0.90), subtalar joint ICC: 0.91 (95% CI 0.88, 0.93) and tendons ICC: 0.96 (95% CI 0.95, 0.97)., Conclusion: A comprehensive and reliable paediatric ankle US scanning protocol and scoring system for the assessment of synovitis and tenosynovitis were successfully developed. Further validation of this scoring system may allow its use as an outcome measure for both clinical and research applications., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To identify differences between baseline Canadian JIA practices and the 2019 ACR guidelines for JIA., Methods: Canadian paediatric rheumatologists were surveyed for their opinions on reasonable a priori target adherence rates for JIA guideline recommendations. Prospectively collected data for 266 newly diagnosed children from 2017 to 2019 were analysed to calculate observed adherence rates. Kaplan-Meier survival curves were used to estimate the cumulative incidence of starting synthetic or biologic DMARDs (sDMARD or bDMARD, respectively) for different patient groups., Results: A total of 25/61 (41%) eligible physicians answered the survey. Most survey respondents (64%) felt that adherence targets should vary depending on the strength of the recommendation and quality of evidence, from a mean of 84% for strong recommendations with high-quality evidence to 29% for conditional recommendations with very low-quality evidence. Data showed 13/19 (68%) recommendations would have met proposed targets and 10/19 (53%) had ≥80% observed adherence. Exceptions were the use of subcutaneous vs oral MTX (53%) and infrequent treatment escalation from NSAIDs to bDMARDs in patients with sacroiliitis (31%) or enthesitis (0%). By 12 weeks, 95% of patients with polyarthritis received sDMARDs, 38% of patients with systemic JIA received bDMARDs and 22% of patients with sacroiliitis received bDMARDs., Conclusion: Canadian paediatric rheumatology practices were in line with many 2019 JIA guideline recommendations before their publication, except for frequent use of oral MTX and infrequent direct escalation from NSAIDs to bDMARDs in sacroiliitis and enthesitis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The aim of this study was to develop and validate a brief disability screen for children with JIA, the Kids Disability Screen (KDS)., Methods: A total of 216 children enrolled in the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry in 2017-2018 formed a development cohort, and 220 children enrolled in 2019-2020 formed a validation cohort. At every clinic visit, parents answered two questions derived from the Childhood Health Assessment Questionnaire (CHAQ): 'Is it hard for your child to run and play BECAUSE OF ARTHRITIS?' ('Hard' 0-10), and 'Does your child usually need help from you or another person BECAUSE OF ARTHRITIS?' ('Help', 0-10). We used 36-fold cross-validation and tested nine different mathematical methods to combine the answers and optimize psychometric properties. The results were confirmed in the validation cohort., Results: Expressed as the mean of the two answers, KDS best balanced ease of use and psychometric properties, while a LASSO regression model combining the two answers with other patient characteristics [estimated CHAQ [eCHAQ]) had the highest responsiveness. In the validation cohort, 22.7%, 25.9% and 28.6% of patients had a score of 0 at enrolment for the KDS, eCHAQ and CHAQ, respectively. Responsiveness was 0.67, 0.74 and 0.62, respectively. Sensitivity to detect a CHAQ > 0 was 0.90 and specificity 0.56, KDS detecting some disability in 44% of children with a CHAQ = 0., Conclusion: This simple KDS has psychometric properties comparable with those of a full CHAQ and may be used at every clinic visit to identify those children who need a full disability assessment., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The COVID-19 pandemic has disrupted healthcare delivery and clinical research worldwide, with data from areas most affected demonstrating an impact on rheumatology care. This study aimed to characterize the impact of the pandemic on the initial presentation of JIA and JIA-related research in Canada., Methods: Data collected from the Canadian Alliance of Pediatric Rheumatology Investigators JIA Registry from the year pre-pandemic (11 March 2019 to 10 March 2020) was compared with data collected during the first year of the pandemic (11 March 2020 to 10 March 2021). Outcomes included time from symptom onset to first assessment, disease severity at presentation and registry recruitment. Proportions and medians were used to describe categorical and continuous variables, respectively., Results: The median time from symptom onset to first assessment was 138 (IQR 64-365) days pre-pandemic vs 146 (IQR 83-359) days during the pandemic. The JIA category frequencies remained overall stable (44% oligoarticular JIA pre-pandemic, 46.8% pandemic), except for systemic JIA (12 cases pre-pandemic, 1 pandemic). Clinical features, disease activity (cJADAS10), disability (CHAQ) and quality of life (JAQQ) scores were similar between the two cohorts. Pre-pandemic, 225 patients were enrolled, compared with 111 in the pandemic year, with the greatest decrease from March to June 2020., Conclusions: We did not observe the anticipated delay in time to presentation or increased severity at presentation, suggesting that, within Canada, care adapted well to provide support to new patient consults without negative impacts. The COVID-19 pandemic was associated with an initial 50% decrease in registry enrolment but has since improved., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The aim was to describe the design, methods and initial findings of a new Canadian inception cohort of children with JIA, The Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) JIA Registry., Methods: The CAPRI JIA Registry was started in 2017 to collect information prospectively on children enrolled within 3 months of JIA diagnosis across Canada. The registry has a non-traditional modular design, with no artificially set times for registry visits to occur, streamlined multi-method data collection that requires 2-4 min per visit, and reports cumulative incidence of treatments, outcomes and adverse events calculated by Kaplan-Meier survival methods., Results: A total of 166 patients, enrolled a median of 6 weeks after JIA diagnosis at 10 centres, were included. The median age at diagnosis was 9 years [interquartile range (IQR) 3, 13], 61% were female and 51% had oligoarticular JIA. The median three-variable clinical Juvenile Arthritis Disease Activity Score was 6.5 (IQR 4, 10) at enrolment, and the median time to first attainment of clinically inactive disease (CID) was 24 weeks (by 1 year, 81%). Within 1 year of diagnosis, 70% of patients had started a DMARD and 35% a biologic agent. The rates of adverse events and serious adverse events were 60 and 5.8 per 100 patient-years, respectively., Conclusion: This streamlined and flexible registry minimizes the burden of data collection and interference with clinic operations. Initial findings suggest that treatments for newly diagnosed patients with JIA in Canada have intensified, and now 81% of patients attain CID within 1 year of diagnosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In aphids, clonal individuals can show distinct morphologic traits in response to environmental cues. Such phenotypic plasticity cannot be studied with classical genetic model organisms such as Caenorhabditis elegans or Drosophila melanogaster. The genetic basis of this biological process remain unknown, as mutations affecting this process are not available in aphids. Here, we describe a protocol to treat third-stage larvae with an alkylating mutagen, ethyl methanesulfonate (EMS), to generate random mutations within the Acyrthosiphon pisum genome. We found that even low concentrations of EMS were toxic for two genotypes of A. pisum. Mutagenesis efficiency was nevertheless assessed by estimating the occurrence of mutational events on the X chromosome. Indeed, any lethal mutation on the X-chromosome would kill males that are haploid on the X so that we used the proportion of males as an estimation of mutagenesis efficacy. We could assess a putative mutation rate of 0.4 per X-chromosome at 10 mM of EMS. We then applied this protocol to perform a small-scale mutagenesis on parthenogenetic individuals, which were screened for defects in their ability to produce sexual individuals in response to photoperiod shortening. We found one mutant line showing a reproducible altered photoperiodic response with a reduced production of males and the appearance of aberrant winged males (wing atrophy, alteration of legs morphology). This mutation appeared to be stable because it could be transmitted over several generations of parthenogenetic individuals. To our knowledge, this study represents the first example of an EMS-generated aphid mutant.

In theory, the loss of sexual reproduction is expected to result in the accumulation of deleterious mutations. In aphids, two main types of life cycle, cyclic and obligate parthenogenesis, represent respectively "sexual" and "asexual" reproductive modes. We used the complete pea aphid genome and previously published expressed sequence tags (ESTs) from two other aphid species. In addition, we obtained 100,000 new ESTs from five more species. The final set comprised four sexual and four asexual aphid species and served to test the influence of the reproductive mode on the evolutionary rates of genes. We reconstructed coding sequences from ESTs and annotated these genes, discovering a novel peptide gene family that appears to be among the most highly expressed transcripts from several aphid species. From 203 genes found to be 1:1 orthologs among the eight species considered, we established a species tree that partly conflicted with taxonomy (for Myzus ascalonicus). We then used this topology to evaluate the dynamics of evolutionary rates and mutation accumulation in the four sexual and four asexual taxa. No significant increase of the nonsynonymous to synonymous ratio or of nonsynonymous mutation numbers was found in any of the four branches for asexual taxa. We however found a significant increase of the synonymous rate in the branch leading to the asexual species Rhopalosiphum maidis, which could be due to a change in the mutation rate or to an increased number of generations implied by its change of life cycle.

Unlabelled: AphidBase aims to (i) store recently acquired genomic resources on aphids and (ii) compare them to other insect resources as functional annotation tools. For that, the Drosophila melanogaster genome has been loaded in the database using the GMOD open source software for a comparison with the 17 069 pea aphid unique transcripts (contigs) and the 13 639 gene transcripts of the Anopheles gambiae. Links to FlyBase and A.gambiae Entrez databases allow a rapid characterization of the putative functions of the aphid sequences. Text mining of the D.melanogaster literature was performed to construct a network of co-cited gene or protein names, which should facilitate functional annotation of aphid homolog sequences. AphidBase represents one of the first genomic databases for a hemipteran insect., Availability: http://w3.rennes.inra.fr/AphidBase.