Acceptability of compounded preparations - A Romanian pediatric hospital perspective.

Compounded medicines are widely used, especially for pediatric patients. The aim of this study was to evaluate children's acceptability of compounded preparations and to provide information regarding compounding practices' characteristics in a Romanian hospital setting. An observational, cross-sectional, and retrospective study was conducted in three Clinical Pediatric Departments (Emergency Clinical Hospital for Children, Cluj-Napoca). The study population comprised patients under 18 years old taking at least one compounded medication. Study data was collected mainly through an interviewer-administered questionnaire and medicine acceptability was assessed based on the children's first reaction to the preparations using a 3-point facial hedonic scale. A total of 162 compounded medications were evaluated. A positive/negative reaction was reported for 20.83%/58.33%, 20.63%/49.21%, and 66.67%/7.41% of oral, oromucosal and cutaneous dosage forms. Although patient disapproval was recorded for various reasons, medication administration was successful in over 75% of cases. Factors such as fewer steps required for intake of a dose, capsule dosage form, no additional food/drink immediately after drug intake, medication perceived as "easy/very easy" to swallow, were correlated with a better acceptability of oral preparations. This study highlights the importance of identifying factors that can improve the acceptability of compounded preparations and, subsequently, treatment outcomes in pediatric patients.

A Pilot Study of Multiplex Ligation-Dependent Probe Amplification Evaluation of Copy Number Variations in Romanian Children with Congenital Heart Defects.

Congenital heart defects (CHDs) have had an increasing prevalence over the last decades, being one of the most common congenital defects. Their etiopathogenesis is multifactorial in origin. About 10-15% of all CHD can be attributed to copy number variations (CNVs), a type of submicroscopic structural genetic alterations. The aim of this study was to evaluate the involvement of CNVs in the development of congenital heart defects. We performed a cohort study investigating the presence of CNVs in the 22q11.2 region and GATA4, TBX5, NKX2-5, BMP4, and CRELD1 genes in patients with syndromic and isolated CHDs. A total of 56 patients were included in the study, half of them (28 subjects) being classified as syndromic. The most common heart defect in our study population was ventricular septal defect (VSD) at 39.28%. There were no statistically significant differences between the two groups in terms of CHD-type distribution, demographical, and clinical features, with the exceptions of birth length, weight, and length at the time of blood sampling, that were significantly lower in the syndromic group. Through multiplex ligation-dependent probe amplification (MLPA) analysis, we found two heterozygous deletions in the 22q11.2 region, both in patients from the syndromic group. No CNVs involving GATA4, NKX2-5, TBX5, BMP4, and CRELD1 genes were identified in our study. We conclude that the MLPA assay may be used as a first genetic test in patients with syndromic CHD and that the 22q11.2 region may be included in the panels used for screening these patients.

Practical Aspects of Upper Gastrointestinal Bleeding in Children.

Upper gastrointestinal bleeding (UGB) in children is a potentially life-threatening condition that represents a challenge for pediatricians and pediatric surgeons. It is defined as bleeding from any location within the upper esophagus to the ligament of Treitz. UGB can have many causes that vary with age. The impact on the child is often proportional to the amount of blood lost. This can range from mild bleeding that is unlikely to cause hemodynamic instability, to massive bleeding that requires admission to the intensive care unit. Proper and prompt management are very important factors in reducing morbidity and mortality. This article aims to summarize current research regarding the diagnosis and treatment of UGB. Most of the data used in the literature published on this subject is extrapolated from adulthood.

PFAPA Syndrome: Clinical, Laboratory and Therapeutic Features in a Single-Centre Cohort.

Objective: The aim of this study is to describe a group of Romanian children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. Materials: This consisted of 39 children diagnosed with PFAPA syndrome according to Thomas' criteria (eight patients with an age at diagnosis <1 year and 31 patients with an age at diagnosis >1 year). Methods: Retrospective analysis of the patients with PFAPA syndrome was focused on clinical features, laboratory findings and therapeutic methods. Comparison between the two groups divided by age at onset was also investigated. Results: Median age at onset was 1.58 years, and median age at diagnosis was 2.97 years. The mean interval between episodes was 35.5 days and the mean duration per febrile episode was 4.1 days. The median diagnosis delay was 2.42 years. The patients presented pharyngitis (100%), adenitis (94.8%) and aphthous lesions (66.7%). The frequency of febrile attacks was higher in children with an age at diagnosis under 1 year (p = 0.0287). Younger age was associated with the presence of aphthae. The mean value of C-reactive protein (CRP) was 7.9mg/dl and the mean value of leucocytes was 14,839/mm3. In 95% of patients given oral corticosteroids, remission of symptoms was reported within 24 h. In three patients, tonsillectomy was performed with complete remission of the disease. Conclusion: We present a cohort of children with PFAPA syndrome, with clinical and laboratory features similar to those described in the literature. Febrile attacks had a higher incidence in children with younger age at the onset of the disease. The patients had a favorable response to corticosteroids.

Anterior and posterior uveitis associated with juvenile idiopathic arthritis -case report.

Anterior uveitis is the most common extra-articular manifestation in children diagnosed with Juvenile idiopathic arthritis (JIA). It is typically a non-granulomatous, chronic, and asymptomatic uveitis. The lack of acute symptoms often delays the diagnosis with the incidence of severe ocular complications. Chorioretinitis lesions have been described in only 1% of cases. The absence of fundus changes can be explained by the impossibility of performing fundoscopy through the cloudy ocular media, secondary to inflammation. A 7-year-old female with a 3-month history of painless reduced vision came to have an eye examination. An initial diagnosis of bilateral anterior granulomatous uveitis complicated with glaucoma and cataract was formulated. Because of the concomitant diagnosis of COVID-19 disease (same day as the eye examination), the child was hospitalized in a hometown COVID-19 patient ward, so both local and general treatment, monitorization, and investigations were discontinued. The following eye examination revealed the persistence of anterior uveitis, inflammatory glaucoma, cataract, and the appearance of band keratopathy. Fundoscopy revealed numerous disseminated lesions of choroiditis. Further examinations established JIA-associated uveitis diagnosis, so systemic corticosteroids were initiated followed by Methotrexate and Adalimumab. Monitoring with fundoscopy in a patient diagnosed with JIA-U is necessary to detect possible chorioretinal or vascular damage. Abbreviations: BVA = best visual acuity, CVA = corrected visual acuity, CS = corticosteroids, IOP = Intraocular pressure, JIA = Juvenile idiopathic arthritis, JIA-U = Juvenile idiopathic arthritis associated uveitis, LE = left eye, MTX = Methotrexate, OU = both eyes, OCT = Optical Coherence Tomography, RE = right eye, TNF = tumor necrosis factor.

Immune Responses to Some Viral Infections That Have a High Evolutionary Potential-A Case Report with Literature Review.

Viral infections are a key issue in modern medicine. SARS-CoV-2 infection confirms that we are not sufficiently prepared for these unforeseen infections. The COVID-19 pandemic has cultivated a great sense of fear and distrust in patients. If viral infections, in this case, SARS-CoV-2, overlap with another infection, the symptoms are prolonged and worsened, and complications may occur. Starting from an objective clinical finding of a patient they had in follow-up and treatment, the authors present the problems of the diseases the patient suffered from. These are described as reviews so that readers can get an idea of the clinical methods of expression and the therapeutic possibilities. Therefore, this article describes Lyme disease and post-treatment Lyme disease syndrome, SARS-CoV-2 infection, and multisystem inflammatory syndrome in children (MISC-C), as the patient suffered from an incomplete form of Kawasaki disease. During the treatment for Lyme disease, the patient also contracted the influenza type A virus. Although any of these diseases could have the potential for serious evolution, our patient still went through these infections relatively well. This can be explained by the fact that the patient had a slow immune response to the aforementioned infections, which allowed him to survive these diseases relatively easily, unlike other individuals who have an exaggerated immune response or who suffer from serious immune involvement, e.g., hepatitis B with a fulminant response. The case was presented chronologically, but at the same time, all particular infection manifestations were accurately described. For these reasons, the article is presented in the form of a review, exemplified by the case itself. Of the 52 cases of MISC-C found in the Pediatrics Clinic II of Cluj-Napoca, we present the case of a male patient who presented with Lyme disease, post-treatment Lyme disease syndrome, Kawasaki disease, and MISC-C incomplete form.

Non-Syndromic Hearing Loss in a Romanian Population: Carrier Status and Frequent Variants in the GJB2 Gene.

The genetic causes of autosomal recessive nonsyndromic hearing loss (ARNSHL) are heterogeneous and highly ethnic-specific. We describe GJB2 (connexin 26) variants and carrier frequencies as part of our study and summarize previously reported ones for the Romanian population. In total, 284 unrelated children with bilateral congenital NSHL were enrolled between 2009 and 2018 in northwestern Romania. A tiered diagnostic approach was used: all subjects were tested for c.35delG, c.71G>A and deletions in GJB6 (connexin 30) using PCR-based methods. Furthermore, 124 cases undiagnosed at this stage were analyzed by multiplex-ligation-dependent probe amplifications (MLPA), probe mix P163, and sequencing of GJB2 exon 2. Targeted allele-specific PCR/restriction fragment length polymorphism (RFLP) established definite ethio-pathogenical diagnosis for 72/284 (25.35%) of the cohort. Out of the 124 further analyzed, in 12 cases (9.67%), we found compound heterozygous point mutations in GJB2. We identified one case of deletion of exon 1 of the WFS1 (wolframin) gene. Carrier status evaluation used Illumina Infinium Global Screening Array (GSA) genotyping: the HINT cohort-416 individuals in northwest Romania, and the FUSE cohort-472 individuals in southwest Romania. GSA variants yielded a cumulated risk allele presence of 0.0284. A tiered diagnostic approach may be efficient in diagnosing ARNSHL. The summarized contributions to Romanian descriptive epidemiology of ARNSHL shows that pathogenic variants in the GJB2 gene are frequent among NSHL cases and have high carrier rates, especially for c.35delG and c.71G>A. These findings may serve in health strategy development.

Laboratory Negative Predictive Factors for the Occurrence of Cardiac Complications in Children with Kawasaki Disease.

BACKGROUND: Patients with Kawasaki disease (KD) may develop cardiovascular complications in the presence of predictive factors, including young age < 6 months, male gender, unfavorable response to intravenous immunoglobulin (IVIG), low albuminemia, thrombocytosis, fever over 8 days, increased C-reactive protein (CRP), elevated levels of 25 OH vitamin D3, elevated levels of fibroblast growth factor 23 (FGF23), elevated D-dimers, elevated ferritin. The objectives of this study were to determine the laboratory negative predictive factors for the occurrence of cardiac complications in children with KD. Studies in the literature that dealt with these predictive factors were analyzed. METHODS: We followed the studies published in PubMed over a 10-year period. Seventy articles were reviewed and, after applying the inclusion and exclusion criteria, 20 articles were selected. RESULTS: We evaluated the population studies which showed factors can predict the occurrence of heart complications. These factors were different depending on age and depending on resistance to IVIG treatment. CONCLUSIONS: Some biological parameters such as low albumin, thrombocytosis, increased CRP, elevated levels of 25 OH vitamin D3, elevated levels of FGF23, elevated D-dimers, and elevated ferritin could be considered as laboratory negative predictive factors for CAL.

Food Allergy a Constant Concern to the Medical World and Healthcare Providers: Practical Aspects.

Food allergy (FA) is a condition with a growing incidence and is a constant concern for the medical world and healthcare providers. With potential symptoms including anaphylaxis, in the event of an allergic reaction the patient's life may well be endangered. The diagnosis of FA is a continuous challenge because mild cases tend to be ignored or diagnosed late and young children with allergies are cared for by parents, who are not always able to accurately interpret symptoms. It is very important to be able to differentiate FAs from food intolerance and toxic reactions to food. An accurate diagnosis is required to provide personalized management of an FA. More sophisticated and accurate diagnostic tests, including component diagnosis and epitope reactivity, allow the provision of a directed diagnosis, a more accurate therapeutic approach, and a useful prognostic evaluation. Tests used in current practice include the specific search for serum IgE, elimination diets, oral food challenges, single, blind, and double-blind (DBPCFC) tests, as well as skin tests. The risk of anaphylaxis can be assessed by molecular diagnostics/component-resolved diagnosis (CRD) and by conducting a basophilic activation test (BAT). These tests allow a planned, personalized treatment based on molecular and clinical profiles. CRD can determine the individual profile of allergic molecular reactivity and enable the formulation of a prognostic judgment. Our article highlights the importance of knowing the immune mechanisms, diagnostics, and immunotherapies in FAs. Starting from observing exposure to food allergens, to identifying allergic reactions, analysing the severity of clinical manifestations, noting the possibilities of diagnosis, and illustrating adequate management strategies.

Quality of Life in Children with Juvenile Idiopathic Arthritis.

Background: The depressive syndrome is commonly found in children suffering from chronic diseases, which is also present in patients with juvenile idiopathic arthritis (JIA). Objective: This study proposed to analyze depression's incidence in children with JIA. We also monitored the evolution of depression with the improvement of the disease under treatment. Material and methods: We followed 145 patients suffering from JIA according to ILAR and Edmonton classification in 2001. The study was conducted over three years between 2015 and 2017. The assessment of depression was made using the Hamilton scale adapted for children by us. This scale consists of 11 fields with multiple questions, the evaluation was made by counting the score. The scale assesses overall depression intensity. It has a maximum score of 28 points, and one with eight points defines depression. Results: The results obtained using the Hamilton scale showed that, from the total of 145 patients suffering from JIA, 35 (24%) experienced mild depression, 10 (7%) moderate depression and 26 were borderline; 74 children did not experience the depressive syndrome. In the control group, depression was found in only 5% of subjects. After administering the most appropriate treatment, symptoms of depression have been improved and the depression score has decreased. Conclusion: The Hamilton questionnaire adapted for children is easy to apply and it is an important tool for assessing depression. Depression has been present in one-third of patients with JIA selected for this study. The symptoms of depression have been correlated with disease activity. Depression does not influence the disease, but the disease induces depression.

Diagnosis and treatment of uveitis associated with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in pediatric population, with uveitis as the most common and severe extra-articular manifestation. Eye damage (bilateral in 70-80% of cases) is usually anterior, chronic and asymptomatic. Young age, female gender, oligoarticular form and ANA positivity are risk factors for chronic anterior uveitis (CAU). Acute anterior uveitis (AAU) frequently occurs in HLA-B27 positive boys with enthesitis-related arthritis. The onset is on average 1.8 years after the onset of JIA, but it may also precede the articular manifestations. Ophthalmological screening for JIA is recommended every 3 or 6-12 months depending on the combination of risk factors for associated uveitis. The major purpose of the treatment is to minimize the loss of visual acuity. The treatment is topical (corticosteroids, cycloplegics) and systemic (short-term glucocorticoids, methotreexate, biological drugs). Biological therapy (indicated if previous treatments are ineffective) is using anti-TNF drugs as first choice (most studies are indicating sup erior efficiency for Adalimumab). Usually AAU is treated promptly and no systemic treatment is needed. In some cases the evolution of CAU can lead to severe complications (synechiaes, cataract, glaucoma, even blindness). Interdisciplinary approach involving the pediatric rheumatologist and ophthalmologist is essential for correct monitoring of this disease.

Different Chronic Disorders That Fall within the Term Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) represents a significant challenge for pediatricians who intend to diagnose and treat this pathology. The classification criteria for JIA subtypes are rigid and often do not fully satisfy the possibilities of classification in the subtype. The objective of this study was to identify clearer criteria for classifying JIA subtypes. The 2019 expert committee meeting (PRINTO) shows the difficulties of this classification and proposes new research directions for the identification of disease subtypes. Four different chronic disorders are used to define JIA in a concise and easy to follow classification system. However, dates from the literature suggest that at least 10% of cases are still difficult to classify. Possibly in the future, different classifications of JIA based on pathophysiological and genetic criteria would be necessary.

A clinical prediction model for estimating the risk of developing uveitis in patients with juvenile idiopathic arthritis.

OBJECTIVE: To build a prediction model for uveitis in children with JIA for use in current clinical practice. METHODS: Data from the international observational Pharmachild registry were used. Adjusted risk factors as well as predictors for JIA-associated uveitis (JIA-U) were determined using multivariable logistic regression models. The prediction model was selected based on the Akaike information criterion. Bootstrap resampling was used to adjust the final prediction model for optimism. RESULTS: JIA-U occurred in 1102 of 5529 JIA patients (19.9%). The majority of patients that developed JIA-U were female (74.1%), ANA positive (66.0%) and had oligoarthritis (59.9%). JIA-U was rarely seen in patients with systemic arthritis (0.5%) and RF positive polyarthritis (0.2%). Independent risk factors for JIA-U were ANA positivity [odds ratio (OR): 1.88 (95% CI: 1.54, 2.30)] and HLA-B27 positivity [OR: 1.48 (95% CI: 1.12, 1.95)] while older age at JIA onset was an independent protective factor [OR: 0.84 (9%% CI: 0.81, 0.87)]. On multivariable analysis, the combination of age at JIA onset [OR: 0.84 (95% CI: 0.82, 0.86)], JIA category and ANA positivity [OR: 2.02 (95% CI: 1.73, 2.36)] had the highest discriminative power among the prediction models considered (optimism-adjusted area under the receiver operating characteristic curve = 0.75). CONCLUSION: We developed an easy to read model for individual patients with JIA to inform patients/parents on the probability of developing uveitis.

The evaluation of heavy metals in transylvania, as predictor for the health status of the exposed population.

It is well known and proven that heavy metal contamination of the soils can severely affect the health of the people living in the contaminated areas given the ease with which trace elements can enter the human body. In addition-to agricultural crop depreciation as well as soil erosion, soil pollution can negatively affect the natural function of ecosystems. While certain heavy metals in high doses can be harmful to the body, others such as cadmium, mercury, lead, chromium, silver and arsenic in minimal amounts have delusional effects on the body, causing acute and chronic intoxication. Our research is focused on the identification of heavy metals from the soil (O, Al, Ca, Cu, Fe, K, Mg, Na, P, Pb, Si, Ti, Zn) in 3 areas in Transylvania where factories were in operation, using 4 methods: UV-VIS spectrometry, AAS, SEM-EDAX and X-ray diffractions. High levels of very toxic trace elements such as lead, aluminum, cadmium were found near the studied areas, especially using SEM-EDAX and AAS methods. Knowledge on the soil concentration of TEs, the time exposure and the side effects can lead us to predict the health status of the exposed population. In our study, by determinating the concentration of TEs we set out to formulate a prediction on the health status of the exposed population using literature data.

Papillary thyroid carcinoma in children with Hashimoto's thyroiditis - a review of the literature between 2000 and 2020.

OBJECTIVES: Thyroid cancer is the most common pediatric endocrine neoplasm representing 3% of all malignancies in children. Hashimoto's thyroiditis (HT) is also a common disorder in the pediatric age range. Patients with HT frequently develop enlarged thyroid with nodules. We aimed to provide a literature review on the frequency of papillary thyroid carcinoma (PTC) in patients with HT. CONTENT: A literature search of the PubMed database between 2000 and 2020 was performed, using the relevant keywords "papillary thyroid carcinoma," "Hashimoto's thyroiditis" and "children". We followed the PRISMA statement guidelines during the preparation of this review. Six studies (n=2,065 patients with HT) were retained for the final analysis. The follow-up of the patients with HT was from 2 to 10 years. PTC was diagnosed in 0.67-7.87% of the HT patients included in these studies. In patients with HT and nodules, the percentage of PTC varied between 5.13 and 35%. The overall occurrence of PTC in patients with HT was 3.07%. SUMMARY AND OUTLOOK: The number of patients developing thyroid nodules in relation to HT was increased. The development of PTC in children with HT appeared to be higher than in the normal population.

Genetic and Environmental Factors in the Pathophysiology of Hashimoto's Thyroiditis.

Finding multiple familial patients with Hashimoto thyroiditis in our clinic a search in the literature confirms that genetic factors, in addition to environmental factors, seem involved in the etiology of this disease.

Unusual Presentation Of Kawasaki Disease With Gastrointestinal And Renal Manifestations.

Diagnosis of Kawasaki disease (KD) is based on well-established clinical criteria. In incomplete or atypical KD, the diagnosis is challenging, because of the paucity of clinical signs or because of the presence of clinical manifestations that generally are not seen in KD. We describe the case of a 3-year-old female patient with persistent high fever, vomiting, watery diarrhea, metabolic acidosis and severe hypopotassemia. On the fourth day of fever, bilateral conjunctivitis, mucous and extremity changes were registered. Urine changes as glycosuria and proteinuria were also noticed. Echocardiography revealed ectasia of the left anterior descending coronary artery, and diagnosis of KD was established. The treatment consisted of intravenous immunoglobulin (IVIG) and oral aspirin. Recurrence of disease was recorded on the 23rd day of the disease, with favorable evolution after the second dose of IVIG was infused.

Bruising as the first sign of exocrine pancreatic insufficiency in infancy.

Exocrine pancreatic insufficiency is an important cause of chronic malnutrition, secondary to maldigestion-malabsorption, which can be caused in children especially by cystic fibrosis, but also by other much rarer diseases. The case of a 6 months and 3 weeks old male pediatric patient is reported, who was admitted to the clinic for head and forearms bruising. Laboratory findings identified vitamin K deficiency as the cause of the cutaneous hemorrhagic syndrome. Further investigations revealed association of steatorrhea (which is a marker of fat malabsorption), iron-deficiency anemia and hypovitaminosis D, which had been produced by nutritional deficiencies caused by malabsorption syndrome. From the numerous disorders that could be associated with pancreatic insufficiency in children, the following conditions had been excluded: cystic fibrosis (mucoviscidosis), cow's milk protein intolerance, gluten-sensitive enteropathy (coeliac disease), Shwachman-Diamond syndrome, abetalipoproteinemia, etc. Based upon decreased levels of stool pancreatic elastase in repeated measurements, together with low serum lipase, the final diagnosis of exocrine pancreatic insufficiency was established. Treatment of this case consisted mainly in pancreatic enzyme replacement therapy, but also oral iron supplementation and dietary supplements with fat-soluble vitamins (A, D, E, K). The outcome was favorable, characterized by normalization of intestinal passage, ascending growth curve and normalization of the majority of laboratory tests values that were modified between the time of patient admission to our clinic and initiation of specific therapy (serum level of vitamin K, vitamin D and lipase, coagulation profile, hemoglobin and red blood cell indexes), as well as higher value of fecal pancreatic elastase.

Phenotypic variability and disparities in treatment and outcomes of childhood arthritis throughout the world: an observational cohort study.

BACKGROUND: To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status. METHODS: In this multinational, cross-sectional, observational cohort study, we asked international paediatric rheumatologists from specialised centres to enrol children with a diagnosis of juvenile idiopathic arthritis, according to International League of Associations for Rheumatology criteria, who were seen consecutively for a period of 6 months. Each patient underwent retrospective and cross-sectional assessments, including measures of disease activity and damage and questionnaires on the wellbeing and quality of life of the children. We qualitatively compared the collected data across eight geographical areas, and we explored an association between disease activity and damage and a country's gross domestic product (GDP) with a multiple logistic regression analysis. FINDINGS: Between April 4, 2011, and Nov 21, 2016, 9081 patients were enrolled at 130 centres in 49 countries, grouped into eight geographical areas. Systemic arthritis (125 [33·0%] of 379 patients) and enthesitis-related arthritis (113 [29·8%] of 379) were more common in southeast Asia, whereas oligoarthritis was more prevalent in southern Europe (1360 [56·7%] of 2400) and rheumatoid factor-negative polyarthritis was more frequent in North America (165 [31·5%] of 523) than in the other areas. Prevalence of uveitis was highest in northern Europe (161 [19·1%] of 845 patients) and southern Europe (450 [18·8%] of 2400) and lowest in Latin America (54 [6·4%] of 849), Africa and Middle East (71 [5·9%] of 1209), and southeast Asia (19 [5·0%] of 379). Median age at disease onset was lower in southern Europe (3·5 years, IQR 1·9-7·3) than in other regions. Biological, disease-modifying antirheumatic drugs were prescribed more frequently in northern Europe and North America than in other geographical settings. Patients living in countries with lower GDP had greater disease activity and damage than those living in wealthier countries. Damage was associated with referral delay. INTERPRETATION: Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographical areas and wealth status of countries. The greater disease burden in lower-resource settings highlights the need for public health efforts aimed at improving equity in access to effective treatments and care for juvenile idiopathic arthritis. FUNDING: IRCCS Istituto Giannina Gaslini.