Delays to Care in Pediatric Lupus Patients: Data From the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry.

OBJECTIVE: Prompt treatment for lupus is important to prevent morbidity. A potential barrier to early treatment of pediatric lupus is delayed presentation to a pediatric rheumatologist. To better understand factors contributing to delayed presentation among pediatric lupus patients, we examined differences in demographic and clinical characteristics of lupus patients within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry with regard to time between symptom onset and presentation to a pediatric rheumatologist. METHODS: We analyzed data from 598 CARRA Legacy Registry participants for differences between those who presented early (withinonset), between 1-3 months (typical presentation), with moderate delays (3-12 months), and with severe delays (≥1 year). Factors associated with early presentation, moderate delay, and severe delay were determined by multinomial logistic regression. RESULTS: Forty-four percent of patients presented early, while 23% had moderate delays and 9% had severe delays. Family history of lupus, absence of discoid rash, and location in a state with a higher density of pediatric rheumatologists were associated with earlier presentation. Younger age, low household income ( CONCLUSION: Delays to care ≥1 year exist in a notable minority of pediatric lupus patients from the CARRA Legacy Registry. In this large and diverse sample of patients, access to care and family resources played an important role in predicting time to presentation to a pediatric rheumatologist

Comparing versions of the memory binding test: Predictive validity for incident aMCI and incident dementia

Background The Memory Binding Test (MBT) Version 1 demonstrated significant predictive validity for incident amnestic MCI (aMCI) and incident dementia. Version 2 of the MBT was developed to be briefer because brevity is essential for screening. Herein we aimed to compare the two versions in terms of predictive validity for aMCI and dementia, separately. Method As sub‐studies of the Einstein Aging Study (EAS), the two MBT versions were administered to two independent study samples between May 2003 and December 2007 at baseline, and these participants were followed up to Jan 2017 (For differences in versions see Table 1). The EAS enrolls a systematically recruited community sample of adults age over 70. The two versions were evaluated in parallel using the same methodologies. We evaluated a range of cut‐scores on the MBT score of choice, the Total Items in the Paired condition (TIP), including the empirical optimal cut‐score which maximized the sum of sensitivity and specificity from the cross‐sectional discriminative analyses. The predictive validity was assessed by Kaplan‐Meier curves, log‐rank tests and Cox regressions. Result Predicting incident aMCI: Both versions were strong predictors of incident aMCI (Table 2): For the empirical optimal scores for TIP, hazard ratio (HR)=2.33, 95% CI: (1.26, 4.29), p=.007 for Version 1, HR=3.38, 95% CI: (1.09, 10.5), p=0.04 for Version 2; for a range of TIP scores (17−22): HR range: 2.27−6.07, p ≤ .01, for Version 1, and 2.67−5.91, p≤.04 for Version 2. Predicting incident dementia: Both versions were strong predictors of incident dementia (Table 3): For the empirical optimal scores for TIP, HR=8.32, 95% CI: (3.51, 19.7), p<.0001 for Version 1, HR=9.30, 95% CI: (3.43, 25.2), p<.0001 for Version 2; for a range of TIP scores (17−23): HR range: 3.09−8.32, p ≤ .003, for Version 1, and 6.40−9.30, p<.0001 for Version 2. Conclusion The predictive validity for incident aMCI and incident dementia was strong and similar for the two versions of the MBT based on the overlapping confidence intervals. These results strongly support the hypothesis that poor performance on memory binding is an important marker for the early detection of aMCI and dementia

Optimizing the memory binding test for detection of aMCI and dementia

Background The Memory Binding Test (MBT) Version 1 demonstrated good discriminative validity for distinguishing persons with dementia and amnestic mild cognitive impairment (aMCI) from cognitively normal elder controls (CN). Version 2 of the MBT test was developed to improve brevity, which is essential for screening. We aimed to compare these two versions in terms of cross‐sectional discriminative validity to distinguish A. aMCI vs. CN, B. aMCI and dementia vs. CN, and C. dementia vs. CN and aMCI. Method Version 1 and Version 2 (for differences see Table 1) of the MBT were administered to independent and systematically recruited samples between May 2003 and December 2007 (Age: 70+; Version 1: 20 dementia cases, 31 aMCI, 246 CN; Version 2: 13 dementia cases, 29 aMCI, 236 CN). Scores on the MBT indices were compared between the versions. The partial area under the receiver operating characteristic curve (ROC AUC) for specificities ≥ 0.70 was compared between indices and versions (Table 1). Specificities were compared between versions when the sensitivity values were comparable. Result The MBT indices were not significantly different between versions for the diagnosis groups of aMCI and dementia. In CN, Version 2 yielded higher scores on number of items Cued Recall for List 1 (CR‐L1), number of Pairs In the Paired condition (PIP), and number of Total Items recalled in the Paired condition (TIP) (14.8±1.5 vs. 14.4±1.7, 11.0±3.2 vs. 9.9±3.8, 26.3±4.0 vs. 24.9±5.0, respectively, p=0.005) and PIP and TIP remained higher (p=0.02) when adjusting for potential confounders of age, gender, education and global cognitive function. Partial AUC comparison shows that TIP was the optimal index for Version 1 and TIP partial AUCs were not significantly different between two versions (Figure 1, Table 2). The specificities were higher in Version 1 vs. Version 2 in Comparisons A and B, while the specificities were comparable in Comparison C (Table 3). Conclusion MBT Version 1 is better at distinguishing aMCI, or aMCI and dementia combined, from cognitively normal elderly. To distinguish dementia vs. cognitively normal elder controls and aMCI, Version 1 and Version 2 are comparable. We recommend using Version 1 for future studies

Tubulointerstitial damage predicts end stage renal disease in lupus nephritis with preserved to moderately impaired renal function: A retrospective cohort study

OBJECTIVES: The presence of tubulointerstitial damage (TID) on renal biopsy is considered to be a late sequela of lupus nephritis (LN). The objective of this study was to determine if TID predicts progression to end stage renal disease (ESRD) in LN patients without advanced kidney disease. METHODS: All SLE patients with an index biopsy consistent with LN between January 2005 and July 2015, and eGFR ≥ 30mL/min/1.73m2 were included. Moderate-to-severe TID was defined as the presence of moderate-to-severe tubular atrophy and/or interstitial fibrosis. Time to ESRD was defined as time from the index biopsy date to incident ESRD date; non-ESRD patients were censored at the time of death or the last visit before December 2015. Time-dependent analyses were conducted to evaluate whether moderate-to-severe TID was predictive of ESRD progression. RESULTS: Of the 131 LN patients with eGFR ≥ 30mL/min/1.73m2, 17 (13%) patients progressed to ESRD. Moderate-to-severe TID was present in 13% of biopsies with eGFR ≥ 60mL/min/1.73m2 and in 33% of biopsies with eGFR between 30 and 60mL/min/1.73m2. Moderate-to-severe TID was associated with a higher risk of ESRD progression: adjusted hazard ratio (HR) = 4.1, 95% CI: 1.4-12.1, p = 0.01 for eGFR ≥ 30mL/min/1.73m2; HR = 6.2, 95% CI: 1.7-23.2, p = 0.008 for eGFR ≥ 60mL/min/1.73m2. There was no association between tubulointerstitial inflammation (TII) and ESRD progression. CONCLUSIONS: Moderate-to-severe TID, but not TII, was a strong predictor of ESRD progression independent of eGFR or glomerular findings, therefore, providing an important window for potential early interventions

Memory Binding Test Distinguishes Amnestic Mild Cognitive Impairment and Dementia from Cognitively Normal Elderly

We aimed to assess reliability and cross-sectional discriminative validity of the Memory Binding Test (MBT) to distinguish persons with amnestic cognitive impairment (aMCI) and dementia from cognitively normal elderly controls. The MBT was administered to 20 participants with dementia, 31 with aMCI and 246 controls, who received the first administration of the MBT from May 2003 to December 2007, as a substudy of the community-based Einstein Aging Study (age range: 70+). The optimal index resulted from comparing the partial area under the receiver operating characteristic curves (ROC AUC) of four major MBT indices for specificities ≥0.70. Optimal cut-score of the optimal index was selected by maximizing the sum of sensitivity and specificity. Age and education effects were assessed using stratified cut-scores and adjusted logistic regression. Reliability was computed as intraclass correlation between scores at baseline and 1-year follow-up for participants who remained cognitively normal. Total number of Items recalled in the Paired condition (TIP) was elected the optimal index. TIP cut-score was ≤22 for differentiating aMCI alone (sensitivity = 0.74, specificity = 0.73) and aMCI and dementia combined (sensitivity = 0.84, specificity = 0.73) from controls. It was ≤17 for differentiating dementia from aMCI and controls (sensitivity = 0.95, specificity = 0.87). Age and education adjustments did not materially improve discriminative validity. The reliability of TIP was 0.77. MBT achieved moderate to good reliability. TIP had superior cross-sectional discriminative validity than the other MBT indices. We recommend using the empirical cut-score of TIP ≤22 for discriminating aMCI and dementia and ≤17 for discriminating dementia alone

Rapid diagnostic testing of hospitalized Malawian children reveals opportunities for improved HIV diagnosis and treatment

Recent World Health Organization (WHO) guidelines recommend antiretroviral therapy (ART) for all HIV-infected people; previously CD4+ T lymphocyte quantification (CD4 count) or clinical staging determined eligibility for children ≥ 5 years old in low- and middle-income countries. We examined positive predictive value (PPV) of a rapid diagnostic test (RDT) algorithm and ART eligibility for hospitalized children with newly diagnosed HIV infection. We enrolled 363 hospitalized Malawian children age 2 months to 16 years with two serial positive HIV RDT from 2013 to 2015. Children aged ≤ 18 months whose nucleic acid testing was negative or unavailable were later excluded from the analysis (N = 16). If RNA PCR was undetectable, human immunodeficiency virus (HIV) enzyme immunoassay (EIA) and western blot (WB) were performed. Those with negative or discordant EIA and WB were considered HIV negative and excluded from further analysis (N = 6). ART eligibility was assessed using age, CD4 count, and clinical HIV stage. Among 150 patients with HIV RNA PCR results, 15 had undetectable HIV RNA. Of those, EIA and WB were positive in nine patients and negative or discordant in six patients. PPV of serial RDT was 90% versus RNA PCR alone and 96% versus combined RNA PCR, EIA, and WB. Of all patients aged ≥ 5 years, 8.9% were ineligible for ART under previous WHO guidelines. Improved HIV testing algorithms are needed for accurate diagnosis of HIV infection in children as prevalence of pediatric HIV declines. Universal treatment will significantly increase the numbers of older children who qualify for ART