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Objective To determine the dose of triptorelin that is sufficient to maintain complete ovarian suppression in female patients with childhood-onset systemic lupus erythematosus (SLE) who require cyclophosphamide therapy, to determine the length of time needed to achieve ovarian suppression after initiation of triptorelin treatment, and to investigate the safety of triptorelin. Methods In this randomized, double-blind, placebo-controlled, dose-escalation study, female patients ages <21 years were randomized 4:1 to receive triptorelin (n = 25) or placebo (n = 6). The starting doses of triptorelin were 25, 50, 75, and 100 μg/kg, and the dose was escalated until complete ovarian suppression was maintained. The primary outcome was the weight-adjusted dose of triptorelin that provided complete ovarian suppression in at least 90% of the patients, as determined by gonadotropin-releasing hormone agonist stimulation testing. The secondary outcome was the period of time required to achieve ovarian suppression, as measured by unstimulated follicle-stimulating hormone and luteinizing hormone levels after the initiation of triptorelin treatment. Results Treatment with triptorelin at a weight-adjusted dose of 120 μg/kg body weight provided sustained complete ovarian suppression in 90% of the patients. After administration of the initial dose of triptorelin, 22 days were required to achieve complete ovarian suppression. The rates of adverse events (AEs) and serious adverse events (SAEs) per 100 patient-months of followup were not higher in the triptorelin group compared with the placebo group (for AEs, 189 versus 362; for SAEs, 2.1 versus 8.5). Conclusion High doses of triptorelin are needed to achieve and maintain complete ovarian suppression, but such doses appear to be well tolerated in adolescent female patients with childhood-onset SLE. Our data suggest that a lag time of 22 days after initiation of triptorelin treatment is required before cyclophosphamide therapy is started or continued. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the reproducibility and validity of the Pediatric Automated Neuropsychological Assessment Metrics (Ped-ANAM) when used in childhood-onset systemic lupus erythematosus (cSLE).Methods: Forty children with cSLE and 40 matched controls were followed for up to 18 months. Formal neuropsychological testing at baseline was repeated after 18 months of followup; overall cognitive performance and domain-specific cognition (attention, working memory, processing speed, and visuoconstructional ability) were measured and categorized as normal cognition, mild/moderate, or moderate/severe impairment. The 10 Ped-ANAM subtests were completed every 6 months and twice at baseline. Ped-ANAM performance was based on accuracy (AC), mean time to correct response (MNc), throughput, and coefficient of variation of the time required for a correct response (CVc) as a measure of response consistency.Results: Particularly, MNc scores demonstrated moderate to substantial reproducibility (intraclass correlation coefficients 0.47-0.80). Means of select Ped-ANAM scores (MNc, AC, CVc) differed significantly between children with different levels of cognitive performance and allowed for the detection of moderate or severe cognitive impairment with 100% sensitivity and 86% specificity. Six Ped-ANAM subtests significantly correlated with the change in overall cognitive function in cSLE (baseline versus 18 months; Spearman's correlation coefficient >0.4, P < 0.05; n = 24).Conclusion: The Ped-ANAM has moderate to substantial reproducibility, criterion and construct validity, and may be responsive to change in cSLE. Additional research is required to confirm the outstanding accuracy of the Ped-ANAM in identifying cognitive impairment, as well as its usefulness in detecting clinically relevant changes in cognition over time. [ABSTRACT FROM AUTHOR]

Objective To explore academic outcomes in childhood-onset systemic lupus erythematosus (cSLE) and their relationship to variables such as demographic and socioeconomic status, neurocognitive functioning, behavioral/emotional adjustment, and cSLE disease status. Methods Forty pairs of children diagnosed with cSLE and healthy best friend controls were rated by parents on a standardized scale of school competence. Information about participants' demographic and socioeconomic status was obtained, along with measures of cSLE disease activity and damage. All of the participants received formal neurocognitive testing and were also rated on standardized scales of behavioral/emotional adjustment and executive functioning. Results Compared to healthy controls, school competence was rated as lower in the cSLE group, although the groups did not differ significantly on indices of cognitive, behavioral, emotional, or executive functioning. School competence ratings were correlated with reading and mathematics achievement test scores in both groups, and with ratings of mental self-regulation in the cSLE group. School competence ratings were correlated with measures of cSLE disease activity and treatment intensity. Conclusion cSLE is associated with inferior parent-rated academic outcomes compared to those noted in demographically-matched peers, despite similar neurocognitive function. The adverse academic outcomes that distinguish children with cSLE from their demographically-matched peers appear to be mediated by SLE disease activity and treatment. [ABSTRACT FROM AUTHOR]

Objective: To define inactive disease (ID) and clinical remission (CR) and to delineate variables that can be used to measure ID/CR in childhood-onset systemic lupus erythematosus (cSLE).Methods: Delphi questionnaires were sent to an international group of pediatric rheumatologists. Respondents provided information about variables to be used in future algorithms to measure ID/CR. The usefulness of these variables was assessed in 35 children with ID and 31 children with minimally active lupus (MAL).Results: While ID reflects cSLE status at a specific point in time, CR requires the presence of ID for >6 months and considers treatment. There was consensus that patients in ID/CR can have <2 mild nonlimiting symptoms (i.e., fatigue, arthralgia, headaches, or myalgia) but not Raynaud's phenomenon, chest pain, or objective physical signs of cSLE; antinuclear antibody positivity and erythrocyte sedimentation rate elevation can be present. Complete blood count, renal function testing, and complement C3 all must be within the normal range. Based on consensus, only damage-related laboratory or clinical findings of cSLE are permissible with ID. The above parameters were suitable to differentiate children with ID/CR from those with MAL (area under the receiver operating characteristic curve >0.85). Disease activity scores with or without the physician global assessment of disease activity and patient symptoms were well suited to differentiate children with ID from those with MAL.Conclusion: Consensus has been reached on common definitions of ID/CR with cSLE and relevant patient characteristics with ID/CR. Further studies must assess the usefulness of the data-driven candidate criteria for ID in cSLE. [ABSTRACT FROM AUTHOR]

The article presents a study which investigated changes in brain activation patterns detected by functional magnetic resonance imaging (FMRI) and the relationship between FMRI activation patterns and results of formal neuropsychological testing in patients with childhood-onset systemic lupus erythematosus (SLE). Results showed that childhood-onset SLE group experienced increased activation of brain areas. The authors said FMRI abnormalities manifest as an imbalance between active and inhibitory responses to an array of stimuli.

Background/Purpose: Childhood-onset lupus (cSLE) is a chronic autoimmune disease and its effect on health-related quality of life (HRQoL) has not been systematically established. The Patient Reported Outcomes Measurement Information System (PROMIS™, ) is a publicly available system to measure patient reported outcomes that features electronic data collection. Although several validated legacy QoL measures exist for cSLE, each is longer than the PROMIS™ Pediatric Short Forms (Short Forms). The objective of this study was to investigate the feasibility, construct and discriminant validity of the Short Forms in cSLE in a clinical setting. Methods: In this ongoing study at two sites, 98 of 100 projected patients completed the Pediatric PROMIS™ Short Forms (Anger, Anxiety, Depressive, Fatigue, Mobility, Upper Extremity, Pain Interference, Peer Relations) and legacy QoL measures (Pediatric Quality of Life Inventory™ Generic Core [GC] & Rheumatology Modules [RM], Simple Measure Of Impact Of Lupus Erythematosus In Youngsters [SMILEY], Childhood Health Assessment Questionnaire [CHAQ], Child Health Questionnaire [CHQ], pain and well-being visual analog scales [VAS]). Questionnaire scores were compared and Spearman correlation analysis was performed in support of the construct validity of the Short Forms when used in cSLE. The discriminant validity was supported by analysis of PROMIS™ and legacy QoL score change at sequential visits and relationship of change was made with Spearman correlation analysis (to be shown). Results: Participants (78% female; 41% White, 44% Black, 6% Asian) had a mean age of 16 yrs (SD 3) and mean SLEDAI score of 6.07 (SD 5.99). There were no problems with completion of any of the PROMIS™ Short Forms (mean score = 50, clinically relevant difference = 10) which required 5-10 minutes in total (legacy QoL tools >15 min. each). On average, cSLE patients scored importantly worse in the Short Form assessing upper extremity function and mobility than the healthy children, while the other QoL domains were less affected (Table ). This is also supported by the scores of the CHQ-PHS. Concurrent validity of the Short Forms is supported by moderate correlations with the scores of various legacy measures (to be shown). [ABSTRACT FROM AUTHOR]

Background/Purpose: Lupus nephritis (LN) is frequently associated with a poor long-term prognosis. Current non-invasive blood and urine tests do not reliably predict the course of LN. The objective of this study was to evaluate the performance of candidate urine biomarkers in predicting future kidney function in adults and children with LN. The biomarker candidates studies were liver-type fatty acid binding protein (L-FABP), albumin (Alb), monocyte chemoattractant protein 1 (MCP-1), Uromodulin, Transferrin and Hepcidin. Methods: L-FABP, Alb, MCP-1, Uromodulin, Transferrin and Hepcidin were measured by ELISA in urine from 70 adults and 42 children collected at the time of enrollment into prospective observational LN cohorts. Urine analytes were normalized to urine creatinine and logarithmically transformed. The association of each analyte to renal function loss (RFL), defined as a sustained increase of ≥25% in serum creatinine (SCr; adults) or a decrease in eGFR of ≥20% (children), was determined using a fixed effect model after adjusting for the age group (adult vs. child). In addition, the results were confirmed using Wilcoxon Rank Sum tests. Logistical models were used to predict the presence of RFL using each biomarker or a combination of the biomarkers. Biomarker performance in predicting RFL was assessed as the area under a ROC curve (AUC) corresponding to the logistical model. Results: 13 children and 22 adults had RFL during the mean follow-up period of 6.1 months and 60 months, respectively. Overall patients with RFL showed significantly higher levels ALB than those without RFL (p < 0.05, ). In addition, the levels of L-FABP, MCP-1, and Transferrin were also marginally higher in RFL (p-values < 0.1). The AUC using the combination of urine L-FABP, Alb, MCP-1 and Utransferrin was 0.66, slightly higher than those using any single biomarker as the predictor (ranging from 0.52-0.63). [ABSTRACT FROM AUTHOR]