Using a representative sample of children with systemic lupus erythematosus (SLE) in the United States, we characterized prescription claim-based hydroxychloroquine and immunosuppressant adherence ...estimates and evaluated their concurrent and predictive validity.
We identified children ages 5–18 with SLE in the Truven Health MarketScan® Commercial and Medicaid claims databases (2013–2018). Among new users of hydroxychloroquine and immunosuppressant medications, we calculated proportion of days covered (PDC) over 365 days to estimate adherence by user group (mycophenolate, azathioprine, methotrexate, and any immunosuppressant use). Agreement between adherence estimates was evaluated with intraclass correlation coefficients (ICC) and kappa statistics. Separate negative binomial regression models were used to estimate associations between (a) hydroxychloroquine, (b) immunosuppressant, or (c) concurrent immunosuppressant/hydroxychloroquine non-adherence and subsequent hospitalizations, adjusted for baseline demographics, disease severity, and healthcare utilization.
Among 423 new hydroxychloroquine/immunosuppressant users, 63% were Medicaid recipients. Sufficient adherence (PDC≥80%) ranged from 33 to 45% for immunosuppressants vs. 51–52% for hydroxychloroquine. Agreement between hydroxychloroquine and immunosuppressant adherence was modest overall, but better for mycophenolate (ICC 0.55) than methotrexate (0.27). Hydroxychloroquine non-adherence was associated with a 2.9-fold higher incidence of subsequent hospitalizations (95% CI 1.2–7.1), whereas immunosuppressant and concurrent non-adherence were associated with 5.9 2.4–14.6 and 5.6-fold 2.0–15.5 increased incidence, respectively. Use of concurrent adherence improved upon estimation of hospitalization risk compared to hydroxychloroquine adherence, but not immunosuppressant adherence alone.
Hydroxychloroquine adherence is an imperfect proxy for adherence to other lupus medications among children with SLE, and therefore assessing immunosuppressant adherence concurrently adds value to hydroxychloroquine adherence assessments. Prescription claims-based immunosuppressant adherence measures are predictive of acute care utilization and may inform population management strategies.
Youth with systemic lupus erythematosus (SLE) transferring from pediatric to adult care are at risk for poor outcomes. We describe patterns of rheumatology/nephrology care and changes in healthcare ...use and medication adherence during transfer.
We identified youth ages 15-25 with SLE using US private insurance claims from Optum's deidentified Clinformatics Data Mart. Rheumatology/nephrology visit patterns were categorized as (1) unilateral transfers to adult care within 12 months, (2) overlapping pediatric and adult visits, (3) lost to followup, or (4) continuing pediatric care. We used negative binomial regression and paired t tests to estimate changes in healthcare use and medication possession ratios (MPR) after the last pediatric (index) visit. We compared MPR between youth who transferred and age-matched peers continuing pediatric care.
Of the 184 youth transferred out of pediatric care, 41.8% transferred unilaterally, 31.5% had overlapping visits over a median of 12 months before final transfer, and 26.6% were lost to followup. We matched 107 youth continuing pediatric care. Overall, ambulatory care use decreased among those lost to followup. Acute care use decreased across all groups. MPR after the index date were lower in youth lost to followup (mean 0.24) compared to peers in pediatric care (mean 0.57, p < 0.001).
Youth with SLE with continuous private insurance coverage do not use more acute care after transfer to adult care. However, a substantial proportion fail to see adult subspecialists within 12 months and have worse medication adherence, placing them at higher risk for adverse outcomes.
BACKGROUNDMacrophage activation syndrome (MAS) is a life-threatening complication of Still's disease (SD) characterized by overt immune cell activation and cytokine storm. We aimed to further ...understand the immunologic landscape of SD and MAS.METHODWe profiled PBMCs from people in a healthy control group and patients with SD with or without MAS using bulk RNA-Seq and single-cell RNA-Seq (scRNA-Seq). We validated and expanded the findings by mass cytometry, flow cytometry, and in vitro studies.RESULTSBulk RNA-Seq of PBMCs from patients with SD-associated MAS revealed strong expression of genes associated with type I interferon (IFN-I) signaling and cell proliferation, in addition to the expected IFN-γ signal, compared with people in the healthy control group and patients with SD without MAS. scRNA-Seq analysis of more than 65,000 total PBMCs confirmed IFN-I and IFN-γ signatures and localized the cell proliferation signature to cycling CD38+HLA-DR+ cells within CD4+ T cell, CD8+ T cell, and NK cell populations. CD38+HLA-DR+ lymphocytes exhibited prominent IFN-γ production, glycolysis, and mTOR signaling. Cell-cell interaction modeling suggested a network linking CD38+HLA-DR+ lymphocytes with monocytes through IFN-γ signaling. Notably, the expansion of CD38+HLA-DR+ lymphocytes in MAS was greater than in other systemic inflammatory conditions in children. In vitro stimulation of PBMCs demonstrated that IFN-I and IL-15 - both elevated in MAS patients - synergistically augmented the generation of CD38+HLA-DR+ lymphocytes, while Janus kinase inhibition mitigated this response.CONCLUSIONMAS associated with SD is characterized by overproduction of IFN-I, which may act in synergy with IL-15 to generate CD38+HLA-DR+ cycling lymphocytes that produce IFN-γ.
Summary Background Limited data are available on the prevalence and predictors of clinical sequelae in survivors of Ebola virus disease (EVD). The EVD Survivor Clinic in Port Loko, Sierra Leone, has ...provided clinical care for 603 of 661 survivors living in the district. We did a cross-sectional study to describe the prevalence, nature, and predictors of three key EVD sequelae (ocular, auditory, and articular) in this cohort of EVD survivors. Methods We reviewed available clinical and laboratory records of consecutive patients assessed in the clinic between March 7, 2015, and April 24, 2015. We used univariate and multiple logistic regression to examine clinical and laboratory features of acute EVD with the following outcomes in convalescence: new ocular symptoms, uveitis, auditory symptoms, and arthralgias. Findings Among 277 survivors (59% female), median age was 29 years (IQR 20–36) and median time from discharge from an EVD treatment facility to first survivor clinic visit was 121 days (82–151). Clinical sequelae were common, including arthralgias (n=210, 76%), new ocular symptoms (n=167, 60%), uveitis (n=50, 18%), and auditory symptoms (n=67, 24%). Higher Ebola viral load at acute EVD presentation (as shown by lower cycle thresholds on real-time RT-PCR testing) was independently associated with uveitis (adjusted odds ratio aOR 3·33, 95% CI 1·87–5·91, for every five-point decrease in cycle threshold) and with new ocular symptoms or ocular diagnoses (aOR 3·04, 95% CI 1·87–4·94). Interpretation Clinical sequelae during early EVD convalescence are common and sometimes sight threatening. These findings underscore the need for early clinical follow-up of survivors of EVD and urgent provision of ocular care as part of health systems strengthening in EVD-affected west African countries. Funding Canadian Institutes of Health Research.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is increasingly affecting pediatric and adult populations. Neuropsychiatric manifestations (ie, cognitive dysfunction and mood ...disorders) appear to occur with greater severity and poorer prognosis in childhood‐onset SLE (cSLE) versus adult‐onset SLE, negatively impacting school function, self‐management, and psychosocial health, as well as lifelong health‐related quality of life. In this review, we describe pathogenic mechanisms active in cSLE, such as maladaptive inflammatory processes and ischemia, which are hypothesized to underpin central phenotypes in patients with cSLE, and the role of alterations in protective central nervous system (CNS) barriers (ie, the blood–brain barrier) are also discussed. Recent findings derived from novel neuroimaging approaches are highlighted because the methods employed in these studies hold potential for identifying CNS abnormalities that would otherwise remain undetected with conventional multiple resonance imaging studies (eg, T2‐weighted or fluid‐attenuated inversion recovery sequences). Furthermore, we propose that a more robust presentation of neuropsychiatric symptoms in cSLE is in part due to the harmful impact of a chronic inflammatory insult on a developing CNS. Although the immature status of the CNS may leave patients with cSLE more vulnerable to harboring neuropsychiatric manifestations, the same property may represent a greater urgency to reverse the maladaptive effects associated with a proneuroinflammatory state, provided that effective diagnostic tools and treatment strategies are available. Finally, considering the crosstalk among the CNS and other organ systems affected in cSLE, we postulate that a finer understanding of this interconnectivity and its role in the clinical presentation in cSLE is warranted.
Abstract
Background
Loss of the normal nocturnal decline in blood pressure (BP), known as non-dipping, is a potential measure of cardiovascular risk identified by ambulatory blood pressure monitoring ...(ABPM). We sought to determine whether non-dipping is a useful marker of abnormal vascular function and subclinical atherosclerosis in pediatric-onset systemic lupus erythematosus (pSLE).
Methods
Twenty subjects 9–19 years of age with pSLE underwent ABPM, peripheral endothelial function testing, carotid-femoral pulse wave velocity/analysis for aortic stiffness, and carotid intima-media thickness. We assessed the prevalence of non-dipping and other ABPM abnormalities. Pearson or Spearman rank correlation tests were used to evaluate relationships between nocturnal BP dipping, BP load (% of abnormally elevated BPs over 24-h), and vascular outcome measures.
Results
The majority (75%) of subjects had inactive disease, with mean disease duration of 3.2 years (± 2.1). The prevalence of non-dipping was 50%, which occurred even in the absence of nocturnal or daytime hypertension. Reduced diastolic BP dipping was associated with poorer endothelial function (
r
0.5,
p
= 0.04). Intima-media thickness was significantly greater in subjects with non-dipping (mean standard deviation score of 3.0 vs 1.6,
p
= 0.02). In contrast, higher systolic and diastolic BP load were associated with increased aortic stiffness (
ρ
0.6,
p
= 0.01 and
ρ
0.7,
p
< 0.01, respectively), but not with endothelial function or intima-media thickness.
Conclusion
In a pSLE cohort with low disease activity, isolated nocturnal BP non-dipping is prevalent and associated with endothelial dysfunction and atherosclerotic changes. In addition to hypertension assessment, ABPM has a promising role in risk stratification and understanding heterogeneous mechanisms of cardiovascular disease in pSLE.
Young adults with childhood-onset rheumatic diseases are more frequently establishing and continuing care with adult rheumatologists. The transfer of care can be challenging for both the young adult ...patients and their adult rheumatologists, in large part due to differences between pediatric-onset rheumatic diseases and their adult-onset counterparts, or due to the rarity of some pediatric-onset rheumatic conditions. Other challenges are due to cultural differences between pediatric and adult medical care and to the young adult needing to increasingly perform self-management skills that were previously managed by parents or other caregivers. In this review, we will provide a summary of strategies for working effectively with young adults as they transition to adult care. We will then discuss a subset of childhood-onset rheumatic diseases-including juvenile idiopathic arthritis, localized scleroderma, autoinflammatory diseases, pediatric-onset systemic lupus erythematosus, juvenile-onset dermatomyositis, and autoimmune encephalitis-for which clinical manifestations, management, and prognosis frequently differ between pediatric onset and adult onset. Our aim is to highlight differences that make caring for this population of transitioning young adults unique, providing tools and knowledge to empower the adult rheumatologist to care for these young adults in ways that are evidence-based, effective, efficient, and rewarding.
There is little data to inform use of renin angiotensin aldosterone system (RAAS) inhibitors in pediatric patients with systemic lupus erythematosus (SLE). Here, we sought to characterize RAAS ...inhibitor use in pediatric SLE and determine whether early RAAS inhibitor initiation among children with incident lupus nephritis is associated with decreased duration of chronic glucocorticoid exposure. A retrospective cohort study was performed of children (ages 5-18) with SLE and/or lupus nephritis in the Truven MarketScan™ Medicaid and Commercial databases (2013-2018) and estimated RAAS inhibitor use. Among incident nephritis cases, we used competing risk hazard models with inverse probability of treatment weighting to estimate the association between RAAS inhibitor initiation less than 180 days after diagnosis and time to glucocorticoid discontinuation with kidney failure as a competing event. Among 592 children with nephritis and 1407 children with non-kidney SLE, 67% and 15% ever received RAAS inhibitors, respectively. Median duration of RAAS inhibitor use among 323 incident users was 14 and 9 months in children with and without nephritis, respectively. Medicaid enrollment was independently associated with greater likelihood of RAAS inhibitor use, irrespective of nephritis. Among 158 incident nephritis cases, early RAAS inhibitor initiation was significantly associated with a faster rate of glucocorticoid discontinuation (adjusted sub-distribution hazard ratio 1.81, 95% confidence interval 1.09 – 3.00). Thus, early initiation of RAAS inhibitors may have a role in children newly diagnosed with lupus nephritis; not only those with refractory proteinuria after induction therapy. Hence, integrated health systems data could be leveraged to confirm these findings and optimize adjunctive therapies in pediatric lupus.
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Objective
Racial and ethnic minority groups have excess morbidity related to renal disease in pediatric‐onset systemic lupus erythematosus (SLE). This study was undertaken to evaluate temporal trends ...in renal outcomes and racial disparities among hospitalized children with SLE over a period of 14 years.
Methods
We identified patients 21 years old or younger with discharge diagnoses of SLE in the Pediatric Health Information System inpatient database (2006–2019). Adverse renal outcomes included end‐stage renal disease (ESRD), dialysis, or transplant, analyzed as a composite and separately. We estimated the odds of adverse renal outcomes at any hospitalization or the first occurrence of an adverse renal outcome, adjusted for calendar period, patient characteristics, and clustering by hospital. We tested whether racial disparities differed by calendar period.
Results
There were 20,893 admissions for 7,434 SLE patients, of which 32%, 16%, 12%, and 8% were Black, Hispanic White, Hispanic Other, and Asian, respectively. Proportions of admissions with adverse renal outcomes decreased over time (P < 0.01). Black children remained at the highest risk of adverse renal outcomes at any admission (odds ratio OR 2.5 95% confidence interval (95% CI) 1.8–3.5 versus non‐Hispanic White patients). Black and Asian children remained at a higher risk of incident adverse renal outcomes, driven by ESRD among Black children (OR 1.6 95% CI 1.2–2.1) and dialysis among Asians (OR 1.7 95% CI 1.1–2.7). Relative disparities did not change significantly over time.
Conclusion
Significant reductions in ESRD and dialysis occurred over time for children with SLE across all racial and ethnic groups. The lack of corresponding reductions in racial disparities highlights the need for targeted interventions to achieve greater treatment benefit among higher risk groups.
There are reports that the incidence of alcohol-involved crashes has remained stable among fatally injured drivers while drug involvement has increased in recent years.
Data from the Fatality ...Analysis Reporting System (FARS) from 2010 to 2013 were used to examine drug and alcohol status of drivers (N = 10 864) of 4-wheeled passenger vehicles involved in a fatal crash while transporting a passenger aged 0 to 14 years (N = 17 179). Mixed effect multivariable logistic regression used SAS GLIMMIX to control for clustering. Odds ratios are reported with 95% confidence intervals (CIs).
Only 28.9% of drivers were screened for both alcohol and drugs, and 56.7% were not tested for either. The total proportion of unrestrained child passengers increased nearly linearly by age. Findings ranged as high as 70% for 13- to 14-year-olds with drivers positive for drugs and alcohol. In multivariable adjusted models, inappropriate child seating with drivers who tested positive was as follows: alcohol, 1.30 (95% CI, 0.92-1.82); drugs, 1.54 (95% CI, 1.24-1.92); and for both drugs and alcohol, 1.88 (95% CI, 1.38-2.55). More than one-fourth were unrestrained with drivers positive for cannabis (27.7%). Overall mortality was approximately triple for unrestrained versus restrained (33.5% vs 11.5%; P < .0001) and was higher in front-seated than rear-seated passengers (40.7% vs 31.5%; P < .0001).
Passengers were less likely to be appropriately seated and to be restrained when transported by a driver positive for drugs and alcohol, but this finding varied according to passenger age and drug/alcohol category.
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