Epigenetic Markers of Renal Function in African Americans

Chronic kidney disease (CKD) is an increasing concern in the United States due to its rapidly rising prevalence, particularly among African Americans. Epigenetic DNA methylation markers are becoming important biomarkers of chronic diseases such as CKD. To better understand how these methylation markers play a role in kidney function, we measured 26,428 DNA methylation sites in 972 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We then evaluated (1) whether epigenetic markers are associated with estimated glomerular filtration rate (eGFR), (2) whether the significantly associated markers are also associated with traditional risk factors and/or novel biomarkers for eGFR, and (3) how much additional variation in eGFR is explained by epigenetic markers beyond established risk factors and biomarkers. The majority of methylation markers most significantly associated with eGFR (24 out of the top 30) appeared to function, at least in part, through pathways related to aging, inflammation, or cholesterol. However, six epigenetic markers were still able to significantly predict eGFR after adjustment for other risk factors. This work shows that epigenetic markers may offer valuable new insight into the complex pathophysiology of CKD in African Americans

Trends in Pediatric Emergency Department Visits for Mental Health Conditions and Disposition by Presence of a Psychiatric Unit

ObjectiveTo examine trends in mental health (MH) visits to pediatric emergency departments (EDs) and identify whether ED disposition varies by presence of a hospital inpatient psychiatric unit (IPU).Study designCross-sectional study of 8,479,311 ED visits to 35 children's hospitals from 2012 to 2016 for patients aged 3 to 21 years with a primary MH or non-MH diagnosis. Multivariable generalized estimating equations and bivariate Rao-Scott chi-square tests were used to examine trends in ED visits and ED disposition by IPU status, adjusted for clustering by hospital.ResultsFrom 2012 to 2016, hospitals experienced a greater increase in ED visits with a primary MH versus non-MH diagnosis (50.7% vs 12.7% cumulative increase, P < .001). MH visits were associated with patients who were older, female, white non-Hispanic, and privately insured compared with patients of non-MH visits (all P < .001). Forty-four percent of MH visits in 2016 had a primary diagnosis of depressive disorders or suicide or self-injury, and the increase in visits was highest for these diagnosis groups (depression: 109.8%; suicide or self-injury: 110.2%). Among MH visits, presence of a hospital IPU was associated with increased hospitalizations (34.6% vs 22.5%, P < .001) and less transfers (9.2% vs 16.2%, P < .001).ConclusionThe increase in ED MH visits from 2012 to 2016 was 4 times greater than non-MH visits at US children's hospitals and was primarily driven by patients diagnosed with depressive disorders and suicide or self-injury. Our findings have implications for strategic planning in tertiary children's hospitals dealing with a rising demand for acute MH care

Rethinking the definition of major trauma: The need for trauma intervention outperforms Injury Severity Score and Revised Trauma Score in 38 adult and pediatric trauma centers

BACKGROUND Patients\u27 trauma burdens are a combination of anatomic damage, physiologic derangement, and the resultant depletion of reserve. Typically, Injury Severity Score (ISS) \u3e15 defines major anatomic injury and Revised Trauma Score (RTS) \u3c7.84 defines major physiologic derangement, but there is no standard definition for reserve. The Need For Trauma Intervention (NFTI) identifies severely depleted reserves (NFTI+) with emergent interventions and/or early mortality. We hypothesized NFTI would have stronger associations with outcomes and better model fit than ISS and RTS. METHODS Thirty-eight adult and pediatric U.S. trauma centers submitted data for 88,488 encounters. Mixed models tested ISS greater than 15, RTS less than 7.84, and NFTI\u27s associations with complications, survivors\u27 discharge to continuing care, and survivors\u27 length of stay (LOS). RESULTS The NFTI had stronger associations with complications and LOS than ISS and RTS (odds ratios [99.5% confidence interval]: NFTI = 9.44 [8.46-10.53]; ISS = 5.94 [5.36-6.60], RTS = 4.79 [4.29-5.34]; LOS incidence rate ratios (99.5% confidence interval): NFTI = 3.15 [3.08-3.22], ISS = 2.87 [2.80-2.94], RTS = 2.37 [2.30-2.45]). NFTI was more strongly associated with continuing care discharge but not significantly more than ISS (relative risk [99.5% confidence interval]: NFTI = 2.59 [2.52-2.66], ISS = 2.51 [2.44-2.59], RTS = 2.37 [2.28-2.46]). Cross-validation revealed that in all cases NFTI\u27s model provided a much better fit than ISS greater than 15 or RTS less than 7.84. CONCLUSION In this multicenter study, NFTI had better model fit and stronger associations with the outcomes than ISS and RTS. By determining depletion of reserve via resource consumption, NFTI+ may be a better definition of major trauma than the standard definitions of ISS greater than 15 and RTS less than 7.84. Using NFTI may improve retrospective triage monitoring and statistical risk adjustments. LEVEL OF EVIDENCE Prognostic, level IV