Perspectives in childhood-onset disabilities: integrating 21st-Century concepts to expand our horizons.

PURPOSE: A powerful aphorism states: "If I hadn't believed it, I wouldn't have seen it!" This challenging notion reminds us how strongly we are influenced by prevailing ideas, and how we interpret things according to current fashions and teachings. MATERIALS AND METHODS: In this paper we present and discuss contemporary perspectives concerning childhood-onset disability and the evolving nature of how people are thinking and acting. We illustrate these ideas by reminding readers of how we have all traditionally been trained and acculturated to think about many dimensions of neurodevelopmental disability ("What?"); reflect on the impact of these ways of thinking in terms of what we have conventionally "seen" and done ("So What?"); and contrast those traditions with contemporary concepts that we believe or know impact the field ("Now What?"). RESULTS: Many of the concepts discussed here will be familiar to readers. In taking this analytically critical perspective we aim to illustrate that by weaving these individual threads together we are able to create a coherent fabric that can serve children with childhood-onset NDD, their families, service providers, the community, and policy-makers. We do not purport to offer a comprehensive view of the whole field. CONCLUSIONS: We encourage readers to consider the integration of these new ways of thinking and acting in our still-evolving field of "childhood-onset disability".

21st-century thinking about childhood-onset neurodisability builds on WHO's ICF framework for health, expanding well beyond traditional primary biomedical foci on diagnosis and management and toward a focus on functioning and belonging.New emphases put family at the centre, attending to family voices and prioritizing family wellbeing as targets for intervention equal to a focus on the child.There is strong emerging evidence to support the value and impact of these broader approaches on overall family functioning and wellbeing.These developments are primarily conceptual rather than technical: they emphasize child and family development, parenting, promotion of functioning, and a life-course approach from the start of intervention.

An uncommon neuroradiological finding of hippocampal malrotation in childhood onset schizophrenia and 22q11.2 Deletion Syndrome: a case report and a brief review of the literature.

Childhood Onset Schizophrenia is a rare neuropsychiatric disorder significantly associated with 22q11.2 Deletion Syndrome. We describe a male patient, followed from childhood to adolescence, who exhibited premorbid impairments in language, learning and social abilities, along with comorbid anxiety disorders. Over time, he gradually developed Childhood Onset Schizophrenia, with neuroradiological findings of white matter hyperintensities, a dysmorphic corpus callosum and Hippocampal Malrotation. These findings were observed in the context of a genetic diagnosis of 22q11.2 Deletion Syndrome, despite the absence of the most common congenital malformations and clinical conditions typically associated with this syndrome. A remarkable aspect of this case report is the emphasis on the importance of suspecting 22q11.2 Deletion Syndrome even in cases where only the neuropsychiatric phenotype of Childhood-Onset Schizophrenia and structural brain alterations, is present. While abnormalities of white matter and corpus callosum are associated with schizophrenia in patients with 22q11.2 Deletion Syndrome, Hippocampal Malrotation is more frequently described in patients with epilepsy and prolonged febrile seizures. Recently, only 10 adult patients with 22q11.2 Deletion Syndrome have been reported to have Hippocampal Malrotation, six of whom were affected by schizophrenia, with or without epilepsy. Our case report aims to extend the neuroradiological findings associated with 22q11.2 Deletion Syndrome and Schizophrenia, including Hippocampal Malrotation. This is the first case report in which Hippocampal Malrotation has been described in Childhood Onset Schizophrenia and 22q11.2 Deletion Syndrome. We suggest that patients with Hippocampal Malrotation and Childhood Onset Schizophrenia, should have a chromosomal microarray performed to screen for 22q11.2 Deletion Syndrome.

Childhood-Onset Systemic Lupus Erythematosus (cSLE): An International Perspective.

PURPOSE OF REVIEW: Childhood-onset systemic lupus erythematosus (cSLE) is a severe and potentially life-threatening chronic autoimmune disease. cSLE is more aggressive and has poorer outcomes than adult-onset disease. The global burden of cSLE is poorly understood, with most publications on cSLE originating from high-resourced settings. The reports from less resourced settings indicate high morbidity and mortality in these populations. RECENT FINDINGS: In this article, we review the disparities in global access to rheumatology care and research for patients with cSLE. We highlight recent cSLE advances from all regions of the globe. We describe current obstacles to cSLE clinical care and research in all settings. Finally, we propose a path forward for high quality, equitable and accessible care to individuals with cSLE everywhere. Individuals with cSLE are at risk for morbidity and death, yet patients worldwide face challenges to adequate access to care and research. Sustained, collaborative efforts are needed to create pathways to improve care and outcomes for these patients.

Education and employment among patients with childhood-onset epilepsy in adulthood: A population-based cohort study.

OBJECTIVE: This study explored the association of childhood-onset epilepsy (COE) with educational attainment, adulthood employment, and income. METHODS: A population-based cohort of 312 children with COE was identified from Tampere University Hospital, Finland. Population Register Center formed a matched random population sample of 1248 children without COE as a reference cohort. The two cohorts were linked to the Statistics Finland database to obtain information on educational attainment, employment status, and income. Fisher's exact test was used to compare employment and graduation. Independent samples t-test was used for analyzing graduation grades and the Mann-Whitney test was used for analyzing yearly income. Results were stratified by sex and disability. RESULTS: During a follow-up of 25 years, a substantially higher proportion of the patients never entered the workforce, 37 % (109/312) compared with 4 % (44/1248) for the referents without COE (p < 0.001). A two-fold difference was observed for COE patients without other disabilities (7.7 %, 13/169, p = 0.01). No clear difference was found in long-term employment between the COE without disabilities and the referents (67 %, 114/169 versus 74 %, 920/1248, p = 0.087). The patients with COE had worse lower secondary school graduation grade averages (7.36 vs 7.6, p = 0.004) and graduation rates (64 % vs 98 %, p < 0.001), the patients without disabilities had similar results to referents (7.43, p = 0.07, 98 %). Of the patients with COE, 18 % graduated from college compared to 38 % of the referents (p < 0.001). The median income was lower in males and females with COE of all ages compared to the referents. The COE patients without additional mental or physical disabilities had income comparable to the healthy referents. 143 patients (46 %) had additional disabilities. SIGNIFICANCE: Patients with COE have lower educational attainment, stable employment, and income. Patients without disabilities also have an increased risk of unemployment, but those capable of entering the workforce have stable careers with earnings comparable to the rest of the population.

Evaluation of thyroid dysfunction in childhood-onset systemic lupus erythematosus: Risk factors for Hashimoto's thyroiditis.

OBJECTIVE: Increased frequency of autoimmune thyroid disease, particularly Hashimoto's thyroiditis (HT) was reported several studies in the literature, in individuals with childhood-onset systemic lupus erythematosus (cSLE). Our study aimed to investigate the prevalence and contributing factors of thyroid dysfunction and HT among cSLE patients. METHODS: Thyroid function tests were obtained cross-sectionally from cSLE patients. Demographic, clinical, and laboratory characteristics and activity scores were collected from medical records. Patients diagnosed with cSLE were compared to the healthy control group for the frequency of thyroid dysfunction. The Mann-Whitney U, independent samples t test, and the Chi-square or Fisher's exact test were used to compare study groups. A p-value below 0.05 was considered statistically significant. RESULTS: Out of 73 cSLE patients, 14 (19.1%) had subclinical hypothyroidism, 9 (12.3%) had clinical hypothyroidism, 12 (16.4%) were diagnosed with HT, and 12 (16.4%) had a family history of HT. Thyroid USG was performed in 5 euthyroid patients and 1 borderline subclinical hypothyroid patient with positive thyroid autoantibody and reported as diffuse heterogeneous echogenicity enlargement in the thyroid gland. There were no significant differences in clinical and laboratory data or medication used between the groups with and without HT; however, patients with HT had a higher frequency of clinical hypothyroidism and family history of HT. Cumulative prednisolone dose was significantly lower in patients diagnosed with HT. The frequency of HT was considerably higher in patients with cSLE compared to the healthy control group. CONCLUSION: The results demonstrate an increased incidence of HT in cSLE patients, even if they are euthyroid, and recommend that cSLE patients be screened more frequently.

A comparison of clinical characteristics and course predictors in early- and childhood-onset schizophrenia.

AIM: The aim of this study was to compare the clinical characteristics of childhood-onset schizophrenia (COS) and early-onset schizophrenia (EOS) during the first- episode psychosis and the stable period, to examine psychopharmacological treatment approaches, and to investigate potential predictive factors for prognosis. METHODS: Demographic, clinical, and psychopharmacological therapy data for 31 patients diagnosed with COS and 66 with EOS were retrieved from the file records in this multicenter study. Symptom distribution and disease severity and course were evaluated twice, in the acute psychotic stage and in the latest stable phase, during follow-up using the positive and negative syndrome scale (PANSS) and clinical global impression (CGI) scales. RESULTS: A statistically significant difference was observed between the groups' CGI improvement rates and median last stable stage PANSS positive, negative, and general psychopathology symptom scores (p = .005, p = .031, p = .005, and p = .012, respectively). Premorbid neurodevelopmental disorder and obsessive-compulsive disorder and comorbidities were more common in the COS group (p = .025 and p = .030, respectively), and treatment required greater multiple antipsychotic use in that group (p = .013). When the independent variables affecting the difference between pre- and post-treatment PANSS scores were examined using linear regression analysis, the model established was found to be statistically significant (F = 5.393; p = .001), and the group variable (p = .024), initial disease severity (p = .001), and socioeconomic level (p = .022; p = .007) emerged as predictive factors for the disease course. CONCLUSION: Although early diagnosis and treatment is an important factor in improving prognosis in schizophrenia, more specific predictors for schizophrenia need to be identified. Additionally, preventive programs and pharmacological methods need to be developed in children with neurodevelopmental problems, particularly those from low socioeconomic status families.

Efficacy and Safety of Pharmacokinetically-Driven Dosing of Mycophenolate Mofetil for the Treatment of Pediatric Proliferative Lupus Nephritis-A Double-Blind Placebo Controlled Clinical Trial (The Pediatric Lupus Nephritis Mycophenolate Mofetil Study).

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 (MMFPK, i.e. the dose is adjusted to the target area under the concentration-time curve (AUC0-12h) of MPA ≥ 60-70 mg*h/L) and MMF dosed per body surface area (MMFBSA, i.e. MMF dosed 600 mg/m2 body surface area), with MMF dosage taken about 12 hours apart. At baseline, subjects are randomized 1:1 to receive blinded treatment with MMFPK or MMFBSA 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 MMFBSA arm with PRR at week 26 will receive MMFPK from week 26 onwards, while subjects with CRR will continue MMFBSA or MMFPK 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 MMFBSA and MMFPK 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.

Capillaroscopy in the daily clinic of the pediatric rheumatologist.

In the last decade, nailfold capillaroscopy is finding its way to the daily clinic of (pediatric) rheumatologist. This review will provide the necessary knowledge for the clinician performing this easy and non-invasive examination in children. In the first part, background information on type of capillaroscopy device and standardized (internationally validated) interpretations for the different capillary variables compared to healthy pediatric controls will be provided. The second part focusses on capillary changes that are observed in Raynaud's phenomenon with follow-up recommendations. This part will also cover capillaroscopy findings in juvenile systemic sclerosis, childhood-onset systemic lupus erythematosus, juvenile dermatomyositis and -mixed connective tissue disease, as well as correlations with disease severity. Lastly, a research agenda shows the current gaps we have in knowledge in this niche of nailfold capillaroscopy in pediatric connective tissue diseases.

Lupus Nephritis Patterns and Response to Type I Interferon in Patients With DNASE1L3 Mutations: Report of Three Cases.

DNASE1L3 is an extracellular nuclease that digests chromatin released from apoptotic cells. DNASE1L3 mutations impair the enzyme function, enhance autoantibody production and type I interferon (IFN-I) responses, and cause different autosomal recessive phenotypes ranging from hypocomplementemic urticarial vasculitis syndrome to full-blown systemic lupus erythematosus (SLE). Kidney involvement in patients with DNASE1L3 mutations is poorly characterised. Herein, we describe the clinical course of three children with monogenic SLE due to DNASE1L3 mutations who developed refractory glomerulonephritis leading to kidney failure. They had different renal histopathological patterns (i.e., membranous, endo- and extra-capillary glomerulonephritis and thrombotic microangiopathy), all belonging to the lupus nephritis (LN) spectrum. One patient had a mixed phenotype, showing an overlap between SLE and ANCA-associated vasculitis. Using immunofluorescence, we detected glomerular expression of the IFN I-induced human myxovirus resistance protein 1 (MXA), which was particularly evident in glomerular endothelial cells. 2/3 patients had increased expression of interferon-stimulated genes in the peripheral blood and all three patients had reduced serum DNAse activity. Our findings suggest that DNASE1L3-related glomerulonephritis can be included in the spectrum of IFN I-mediated kidney disorders, and provide the rationale for IFN I-directed therapies in order to improve the poor outcome of this rare condition.

The TRUST Study-TRansition US Together: Evaluating the Impact of a Parent- and Adolescent-Centered Transition Toolkit on Transition Readiness in Patients with Juvenile Idiopathic Arthritis and Childhood-Onset Systemic Lupus Erythematosus.

OBJECTIVE: Adolescents with chronic rheumatic disease must increasingly take on more responsibility for disease management from parents as they transition from pediatric to adult care. Yet, there are limited resources to inform and support parents about transition. Here, we evaluate the impact of a Transition Toolkit, geared towards parents and adolescents, on transition readiness, and explore the potential impact of parent-adolescent communication. METHODS: A prospective cohort study of youths aged 14-18 years old and their parents was performed. Participant demographics, disease characteristics, transition readiness scores (Transition-Q, max 100), and parent-adolescent communication scores (PACS, max 100) were collected at enrollment (when the Transition Toolkit was shared with adolescents and their parents. Generalized estimating equation (GEE) analyses determined the influence of the Toolkit on transition readiness and explored the role of parent-adolescent communication quality. Subgroup analyses were conducted by sex. RESULTS: A total of 21 patients were included; 19 completed one post-intervention Transition-Q and 16 completed two. Transition-Q scores increased over time and the rate of increase doubled after the Toolkit was shared (ß = 7.8, p < 0.05, and ß = 15.5, p < 0.05, respectively). CONCLUSION: Transition readiness improved at each follow-up, the greatest increase was seen after the Toolkit was shared. Parent-adolescent communication quality did not appear to impact changes in transition readiness.

Childhood-onset systemic lupus erythematosus: A descriptive and comparative study of clinical, laboratory, and treatment characteristics in two populations.

OBJECTIVE: The aim of this study was to characterize childhood-onset systemic lupus erythematosus (SLE) in two large cohorts from Turkey and the United States. METHODS: Patients diagnosed with childhood-onset SLE who fulfilled the 1997 American College of Rheumatology classification criteria for SLE from four reference centers in Turkey and the University of Pittsburgh School of Medicine in the United States were included in this study. A comparative analysis was conducted to evaluate the similarities and differences in clinical and laboratory features, damage accrual, and treatment experiences between the two populations. RESULTS: A total of 174 patients with childhood-onset SLE were included in this study (108 patients from Turkey and 66 patients from the United States). The female-to-male ratio was similar between the two cohorts (∼3:1, p = .73). The median age at diagnosis was 11.67 years (2.19-17.93) in the Turkish cohort and 13.68 years (2.74-17.93) in the U.S. cohort (p < .001). Photosensitivity (45.4% and 21.2%; p = .007) and renal involvement (41.7% and 36.4%; p = .045) were higher in the Turkish cohort. Anti-Ro/SSA (34.8% and 15.7%; p < .001), anti-Sm (59.1% and 19.4%; p < .001), and anti-RNP (47.0% and 14.8%; p < .001) positivity was more frequent in the U.S. cohort. Current use of rituximab (37.9% and 1.9%; p < .001) and belimumab (19.7% and 0%; p < .001) was more prevalent in the U.S. cohort, while the use of cyclophosphamide (often according to the low dose Euro-Lupus protocol) throughout the disease course (24.1% and 4.5%; p < .001) was more frequent in the Turkish cohort. SLICC/ACR Damage Index scores were not different between the two cohorts. CONCLUSION: This study provides detailed clinical and laboratory features of childhood-onset SLE in two independent and geographically divergent cohorts. Our findings suggest an earlier age of disease onset and a higher prevalence of kidney involvement in Turkish patients. Differences in treatment approaches were also noted. However, damage accrual related to SLE does not appear to be different between the two patient populations.

Conceptualization, use, and outcomes associated with compassion in the care of youth with childhood-onset disabilities: a scoping review.

Introduction: To examine the scope of existing literature on the conceptualization, use, and outcomes associated with compassion in the care of youth with childhood-onset disabilities. Methods: A protocol was developed based on the Joanna Briggs Institute (JBI) scoping review method. MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and EBSCOhost CINAHL, were searched. Results: Eight studies were selected for inclusion; four used quantitative methodology, and four used qualitative methods. Compassion was not defined a priori or a posteriori in any of the included studies. The concept of self-compassion was explicitly defined only for parents of youth with childhood-onset disabilities in three studies a priori. The most reported outcome measure was self-compassion in parents of youth with childhood-onset disabilities. Self-compassion among parents was associated with greater quality of life and resiliency and lower stress, depression, shame and guilt. Discussion: There is limited evidence on the conceptualization, use, and outcomes associated with compassion among youth with childhood-onset disabilities. Self-compassion may be an effective internal coping process among parents of youth with childhood-onset disabilities. Further research is required to understand the meaning of compassion to youth with childhood-onset disabilities, their parents and caregivers. Systematic review registration: https://doi.org/10.17605/OSF.IO/2GRB4.

First Cousin Marriages and the Risk of Childhood-Onset Vitiligo: Exploring the Genetic Background: A Cross-Sectional Study.

Background: Vitiligo, a condition characterized by depigmented skin, has been observed to have a higher incidence in patients with a family history of the disease. This study investigates the relationship between parental consanguinity, family medical history, and the onset of childhood vitiligo, hypothesizing that genetic factors play a significant role. Methods: A cross-sectional study was conducted involving 382 people diagnosed with vitiligo in Saudi Arabia. The study assessed the prevalence of parental consanguinity and its correlation with the disease's onset, employing statistical analysis to evaluate the data collected through medical records and family history questionnaires. Results: The findings reveal a significant association between parental consanguinity, particularly among first cousins, and the incidence of childhood-onset vitiligo. Additionally, a notable correlation was found between family medical history and the onset of the condition, with familial vitiligo being more prevalent in patients with adult-onset vitiligo. Conclusion: This study underscores the critical role of genetic predispositions in the development of childhood-onset vitiligo, highlighting the influence of parental consanguinity. The results advocate for increased awareness and screening in populations with high rates of consanguinity to facilitate early detection and management of vitiligo. Future research should focus on exploring the genetic mechanisms underlying this association to develop targeted interventions.

Does the esv3587290 Copy Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican Childhood-Onset Systemic Lupus Erythematosus Patients?

A ~3-kb deletion-type DNA copy number variation (CNV, esv3587290) located at intron 7 of the VANGL1 gene (1p13.1, MIM*610132) has been proposed as a genetic factor in lupus nephritis (LN) development in adult systemic lupus erythematosus (SLE) patients across European-descent populations, but its replication in other ethnicities has been inconsistent and its association with LN in childhood-onset SLE (cSLE) remains unknown. Here, we performed an exploratory association study in a sample of 66 unrelated cSLE Mexican patients (11 males, 55 females; ages 7.8 to 18.6 years). Two stratified groups were compared: cSLE patients with (N = 39) or without (N = 27) LN, as diagnosed by renal biopsy (N = 17), proteinuria (N = 33), urinary protein-creatinine ratio > 0.2 (N = 34), and erythrocyturia and/or granular casts in urinary sediment (N = 16). For esv3587290 CNV genotyping, we performed an end-point PCR assay with breakpoint confirmation using Sanger sequencing. We also determined the allelic frequencies of the esv3587290 CNV in 181 deidentified ethnically matched individuals (reference group). The obtained genotypes were tested for Hardy-Weinberg equilibrium using the χ2 test. Associations between LN and esv3587290 CNV were tested by calculating the odds ratio (OR) and using Pearson's χ2 tests, with a 95% confidence interval and p ≤ 0.05. The esv3587290 CNV allele (OR 0.108, 95% CI 0.034-0.33, p = 0.0003) and the heterozygous genotype (OR 0.04, 95% CI 0.119-0.9811, p = 0.002) showed a significant protective effect against LN development. Finally, we characterized the precise breakpoint of the esv3587290 CNV to be NG_016548.1(NM_138959.3):c.1314+1339_1315-897del in our population. This report supports the notion that a broad genetic heterogeneity underlies the susceptibility for developing LN.

IFN-I Score and Rare Genetic Variants in Children with Systemic Lupus Erythematosus.

Introduction: Interferon I (IFN I) signaling hyperactivation is considered one of the most important pathogenetic mechanisms in systemic lupus erythematosus (SLE). Early manifestation and more severe SLE courses in children suggest a stronger genetic influence in childhood-onset SLE (cSLE). Aim: To evaluate IFN-I score and SLE-associated genetic variants in cSLE. Material and Methods: 80 patients with cSLE were included in the study. IFN I-score was assessed by real-time PCR quantitation of 5 IFN I-regulated transcripts (IFI44L, IFI44, IFIT3, LY6E, MXA1) in 60 patients. Clinical exome sequencing (CES) was performed in 51 patients. Whole-exome sequencing was performed in 32 patients with negative results of CES. Results: 46/60 patients (77%) had elevated IFN-I scores. Leucopenia and skin involvement were associated with over-expression of IFI44 and IFI44L, while hypocomplementemia-with hyperactivation of IFIT3, LY6E, and MX1. No correlation of IFN-I score with disease activity was found. At least one rare genetic variant, potentially associated with SLE, was found in 29 (56.9%) patients. The frequency of any SLE-genetic variants in patients with increased IFN scores was 84%, in patients with normal IFN scores-33%, and in the group whose IFN score was not assessed was 65% (p = 0.040). The majority of genetic variants (74%) are functionally related to nucleic acid sensing and IFN-signaling. The highest frequency of genetic variants was observed in Sakha patients (9/14; 64.3%); three and two unrelated patients had identical variants in PTPN22 and TREX1 genes, respectively. Conclusions: More than half of patients with childhood-onset SLE have rare variants in SLE-associated genes. The IFN-I score could be considered a tool for the selection of patients for further genetic assessment in whom monogenic lupus is suspected.

Nationwide Survey on Transitional Care for Patients With Childhood-Onset Cardiomyopathy in Japan.

Background: Individuals transitioning into adulthood require age-appropriate medical care and delegation of decision-making authority from their parents to the patients themselves. Although there have been multiple observational and interventional studies on transitional care for patients with congenital heart disease (CHD) in the cardiovascular field, transitional care specific to childhood-onset cardiomyopathy (CM) remains unaddressed. Methods and Results: A nationwide questionnaire-based survey was performed in the pediatric cardiology departments of 151 facilities in Japan. Responses were obtained from 100 (66%) facilities with low transfer rates (<5%) for childhood-onset CM cases. The comparison between CHD-transferring and non-CHD-transferring facilities revealed a significantly higher transfer rate (83.9%) for childhood-onset CM cases in the CHD-transferring facilities (P<0.001). Regarding the transition programs, 72 (72%) facilities do not offer any programs for CM, while most (92%) facilities recognize its necessity. Finally, only 19 (19%) facilities provided a transition program, 10 of which were CHD based. Conclusions: To the best of our knowledge, this is the first study to demonstrate the poor transition/transfer care status of patients with childhood-onset CM in Japan. The transfer rate of CMs was lower than that of CHDs, and transition programs were less available. Referring to the system established for CHD could help develop a successful transitional care system for CM.

A co-designed mixed methods study on community-based gym exercise for non-ambulant adults with childhood onset disability.

PURPOSE: Explore community-based gym exercise for non-ambulant adults with childhood-onset disability. MATERIALS AND METHODS: Non-ambulant adults with childhood-onset disability participated in four, weekly gym sessions co-facilitated by physiotherapists and exercise professionals. Practicalities of participating in the sessions were recorded via uptake and attrition, weekly surveys, and focus groups. Perspectives of those who designed/delivered the study were gathered via weekly debrief meetings. Quantitative data were analysed descriptively, qualitative data were analysed thematically. RESULTS: Ten non-ambulant adults with childhood-onset disability participated; 70% completed all exercise sessions. Focus groups identified three themes. "I wouldn't be able to exercise…there's no option for a community-based setting" described the lack of opportunities for exercise in gyms. "You don't realise the benefit of coming here" highlighted benefits of exercise. "We can do better" had two sub-themes: problem solving and ingredients for community-based gym exercise. Weekly feedback and debrief meetings identified practicalities related to equipment, exercises, and collaborative working between facilitators. CONCLUSIONS: Whilst there is an interest in community-based gym exercise for non-ambulant adults with childhood-onset disability, there remains a lack of inclusive gyms. Co-design of inclusive gym guidelines and condition-specific physical activity referral scheme may enhance opportunities for participation in gym exercise for adults with childhood-onset disability.

Adults with non-ambulant childhood-onset disability want to access gyms to self-manage their condition.Accessible facilities and provision of dignified toileting would reduce the barriers to participation in community-based gym exercise for non-ambulant adults with childhood-onset disability.Specialist rehabilitation staff and support are necessary to facilitate participation in community-based gym exercise by non-ambulant adults with childhood-onset disability.

Relationship of regional ultraviolet index data with rash and systemic disease activity in youth with childhood-onset systemic lupus: results from the Childhood Arthritis and Rheumatology Research Alliance Registry.

OBJECTIVE: To investigate the association between ultraviolet light index (UVI), as a marker for UV exposure, and seasonality with rash and systemic disease activity in youth with childhood-onset systemic lupus (cSLE) from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. METHODS: We reviewed data on rash and disease activity from Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores from cSLE CARRA Registry participants with visits between 2010 and 2019 and obtained zipcode level UVI data from the National Oceanic and Atmospheric Administration (NOAA). Our main exposures were UVI and season during the month of visit and one month prior to visit. We used mixed-effects logistic regression models to examine associations between regional UVI (by zipcode)/season and odds of rash and severe SLEDAI-2 K score (≥ 5 vs. 0-4), adjusting for age, sex, race and income. RESULTS: Among 1222 participants, with a mean of 2.3 visits per participant, 437 visits (15%) had rash and 860 (30%) had SLEDAI-2 K score ≥ 5. There were no associations between UVI during the month prior to visit or the month of the visit and odds of rash or elevated systemic activity. However, fall season was associated with increased odds of rash (OR = 1.59, p = 0.04), but not increased disease activity. CONCLUSION: This study found no association between UVI and rash or UVI and disease activity. However, further studies directly measuring UV exposure and accounting for patient-level protective behavioral measures may help to better understand the complex relationship between sun exposure and SLE disease activity.

Higher incidence of paediatric inflammatory bowel disease by increasing latitude in Norway, but stable incidence by age.

AIM: To examine possible geographical and temporal differences in the incidence of childhood-onset inflammatory bowel disease (IBD) in Norway, motivated by previous research indicating relevant environmental factors explaining changing epidemiology. METHODS: We analysed data from children born in Norway from 2004 to 2012 (n = 541 036) in a registry-based nationwide study. After validating registry diagnoses against medical records, we defined IBD as ≥2 entries of International Classification of Diseases, 10th revision (ICD-10) codes K50, K51 and K52.3 in the Norwegian Patient registry. We estimated hazard ratios (HR) for IBD across four geographical regions with a south-to-north gradient and the incidence by period of birth. RESULTS: By the end of follow-up on 31 December 2020, 799 IBD diagnoses were identified (Crohn's disease: n = 465; ulcerative colitis, n = 293, IBD: unclassified, n = 41). Compared to children in the southernmost region, there was almost a two-fold HR for IBD in children in the most Northern region (HR = 1.94, 95% Cl = 1.47-2.57; Mid region: HR = 1.68, 95% CI = 1.29-2.19, ptrend <0.001). These estimates remained largely unchanged after adjustment for potential confounding factors. The cohorts born in 2004-2006 and 2010-2012 had comparable cumulative incidences, with a slightly higher incidence for those born in 2007-2009. CONCLUSION: We observed an increase in the risk of IBD by increasing latitude which may suggest that environmental factors influence the development of IBD, although non-causal explanations cannot be ruled out.

Detailed Clinical Features of PTPRQ-Associated Hearing Loss Identified in a Large Japanese Hearing Loss Cohort.

The PTPRQ gene has been identified as one of the genes responsible for non-syndromic sensorineural hearing loss (SNHL), and assigned as DFNA73 and DFNB84. To date, about 30 causative PTPRQ variants have been reported to cause SNHL. However, the detailed clinical features of PTPRQ-associated hearing loss (HL) remain unclear. In this study, 15,684 patients with SNHL were enrolled and genetic analysis was performed using massively parallel DNA sequencing (MPS) for 63 target deafness genes. We identified 17 possibly disease-causing PTPRQ variants in 13 Japanese patients, with 15 of the 17 variants regarded as novel. The majority of variants identified in this study were loss of function. Patients with PTPRQ-associated HL mostly showed congenital or childhood onset. Their hearing levels at high frequency deteriorated earlier than that at low frequency. The severity of HL progressed from moderate to severe or profound HL. Five patients with profound or severe HL received cochlear implantation, and the postoperative sound field threshold levels and discrimination scores were favorable. These findings will contribute to a greater understanding of the clinical features of PTPRQ-associated HL and may be relevant in clinical practice.