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Objective Determine the pharmacokinetics (PK) and exposure–response of hydroxychloroquine (HCQ) and desethylhydroxychloroquine (DHCQ) in paediatric SLE (pSLE).Methods We conducted an exploratory phase 2, direct-to-family trial. Children enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry with a diagnosis of pSLE were eligible if they were receiving HCQ as standard of care for ≥3 months. Biological samples were collected at up to four visits over a 6-month period. At each visit, plasma was obtained to measure the concentrations of HCQ and DHCQ, as well as cytokines. HCQ and DHCQ plasma PK data were analysed using a population PK modelling approach.Results Twenty-five subjects provided a total of 88 plasma concentrations for PK analysis. There was a poor linear fit between HCQ concentrations and total body weight (R2=0.03). There was a decline in both interferon (IFN)-alpha and IFN-gamma with higher concentrations of HCQ and DHCQ. Volume of distribution for HCQ in plasma was higher in children compared with published values in adults (73 000 L vs 44 000 L), but clearance values in children were similar to adults.Conclusions We report the first population PK model for HCQ and DHCQ in children using data from a novel direct-to-family clinical trial. We observed high interindividual variability in HCQ PK and found that weight-based dosing for HCQ is poorly correlated with drug concentrations, suggesting the need to use therapeutic drug monitoring to individualise dosing. Furthermore, our results suggest that the current weight-based dosing paradigm for HCQ may result in suboptimal drug exposures, particularly for children with obesity. Accordingly, additional studies of HCQ are needed in pSLE to determine the optimal drug concentration and dosing to reduce disease activity and improve outcomes.Trial registration number NCT04358302.

Competing Interests: CC is funded by a grant from the National Institute of Health Research. KB is supported by the Czech Ministry of Health (DRO FNOl, 00098892). The other authors declare no competing interests.

Background: The safety and efficacy of mycophenolate mofetil (MMF) for lupus nephritis (LN) treatment is established in adults and in some children. MMF is rapidly converted to the biologically active metabolite mycophenolic acid (MPA) whose pharmacokinetics (PK) is characterized by large inter- and intra-individual variability., Methods/design: This randomized, double-blind, active comparator, controlled clinical trial of pediatric subjects with proliferative LN compares pharmacokinetically-guided precision-dosing of MMF (MMF PK , i.e. the dose is adjusted to the target area under the concentration-time curve (AUC 0-12h ) of MPA ≥ 60-70 mg*h/L) and MMF dosed per body surface area (MMF BSA , i.e. MMF dosed 600 mg/m 2 body surface area), with MMF dosage taken about 12 hours apart. At baseline, subjects are randomized 1:1 to receive blinded treatment with MMF PK or MMF BSA for up to 53 weeks. The primary outcome is partial clinical remission of LN (partial renal response, PRR) at week 26, and the major secondary outcome is complete renal response (CRR) at week 26. Subjects in the MMF BSA arm with PRR at week 26 will receive MMF PK from week 26 onwards, while subjects with CRR will continue MMF BSA or MMF PK treatment until week 53. Subjects who achieve PRR at week 26 are discontinued from study intervention., Discussion: The Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) study will provide a thorough evaluation of the PK of MMF in pediatric LN patients, yielding a head-to-head comparison of MMF BSA and MMF PK for both safety and efficacy. This study has the potential to change current treatment recommendations for pediatric LN, thereby significantly impacting childhood-onset SLE (cSLE) disease prognosis and current clinical practice.

Background: Given the impact of psychological factors on rheumatic disease, pediatric psychologists serve a vital role in promoting quality of life and managing common problems among youth with rheumatic disease. The aim of this project was to increase access to psychological services among youth with rheumatic disease at a children's hospital., Methods: A quality improvement (QI) team identified key drivers and interventions aimed to increase access to psychological services for youth with rheumatic disease. Data was collected for a 6-month baseline period and 4-year intervention period. We applied the Plan-Do-Study Act method of QI and the American Society for Quality criteria to adjust the center line and control limits., Results: There were two statistically significant center line shifts in the number of patients seen by psychology and one statistically significant shift in referrals to psychology over time with applied stepwise interventions. Patients seen by a psychologist increased by 3,173% from a baseline average of 1.8 to 59.9 patients seen per month (p < 0.03). Psychology referrals increased by 48% from a baseline average of 9.85 to 14.58 referrals per month over the intervention period (p < .01)., Conclusions: Youth with rheumatic disease received increased access to mental health treatment when psychological services were imbedded within rheumatology care. Psychology referrals also increased significantly, suggesting that psychology integration within a medical clinic can increase identification of needs. Results suggest that psychology integration into rheumatology care may increase access to mental health treatment and identification of psychological needs in this at-risk population., (© 2023. The Author(s).)

This article offers a summary, synthesis, and highlights of processes, surveys, summits, and discussions among members of the Society for the Study of School Psychology exploring current and historical perspectives as to a potential definition of school psychology research. After multiple revisions, the final definition is as follows: School psychology research is the systematic investigation of phenomena concerning the educational, emotional, behavioral, and social outcomes, as well as the school, family, and societal systems in which these outcomes are imbedded. It is principally concerned with socially responsive implementation and translating research into equitable practices that can lead to improved functioning of students, families, schools, and community systems that support educational and psychological services. It includes basic and applied research and theory development that focuses on a wide array of topics including, for example, prevention, intervention, assessment, diagnosis, diversity, equity and inclusion, measurement, methodology, statistics, and professional issues. This wide range of topics is informed by diverse theories arising from a broad array of disciplines and investigated by researchers from a variety of educational and scientific backgrounds. Common to all of the areas of research inquiry is a focus on enhancing student, family, and community outcomes-particularly educational and social outcomes of all students-and in building the capacity of systems (schools, communities, and other systems) to support those outcomes with a commitment to incorporating social responsiveness in the research process. The aim of this definition is to embrace the breadth of scholarship informing and advancing the science, practice, and policy relevant to the field of school psychology., (Copyright © 2022. Published by Elsevier Ltd.)