Increase in Rate of Hospitalizations for Pediatric Intentional Acetaminophen Ingestion at a Single Center During the COVID-19 Pandemic.

OBJECTIVES: Social disruption due to COVID-19 has detrimentally affected American adolescents' emotional well-being. Within our system, pediatric acetaminophen ingestions increased in 2020, compared with previous years. We sought to evaluate the rate of hospitalizations for acetaminophen self-harm ingestions and self-harm of adolescents during the COVID-19 pandemic. STUDY DESIGN: We identified patients (aged 0-23) from billing data with diagnosis of acetaminophen ingestion with self-harm intent (ICD-10 code T391X2A), from a multicenter urban, quaternary health care system. We performed retrospective chart review from 2016 to 2020 and performed statistics using a generalized estimating equation (GEE) logistic regression model. RESULTS: From 2016 to 2020, there were 25 790 discharges of adolescents with 65 acetaminophen self-harm ingestion and 148 self-harm discharges. Of the 65 acetaminophen patients, 75% identified as female and 54% identified as non-white; 71% with Medicaid insurance. The proportion of acetaminophen ingestion and self-harm admissions increased from 0.13% in 2016 to 0.46% by 2020 and 0.42% in 2016 to 0.73% by 2020, respectively. The odds of acetaminophen ingestion admission increased by 28% each additional year (odds ratio = 1.28; 95% confidence interval: 1.08, 1.53; P = .006). There was not enough evidence to conclude that the log-odds of a self-harm ingestion were linearly related to time (P = .06). CONCLUSIONS: Acetaminophen ingestion for self-harm has significantly increased, while overall self-harm has increased to a lesser, nonsignificant degree. Primarily females of color and those with Medicaid insurance are affected. It is important to note this growing, disturbing trend, and to continue to screen for depression in our adolescent community and ensure access to mental health resources.

Sclerostin inhibition reverses skeletal fragility in an Lrp5-deficient mouse model of OPPG syndrome.

Osteoporosis pseudoglioma syndrome (OPPG) is a rare genetic disease that produces debilitating effects in the skeleton. OPPG is caused by mutations in LRP5, a WNT co-receptor that mediates osteoblast activity. WNT signaling through LRP5, and also through the closely related receptor LRP6, is inhibited by the protein sclerostin (SOST). It is unclear whether OPPG patients might benefit from the anabolic action of sclerostin neutralization therapy (an approach currently being pursued in clinical trials for postmenopausal osteoporosis) in light of their LRP5 deficiency and consequent osteoblast impairment. To assess whether loss of sclerostin is anabolic in OPPG, we measured bone properties in a mouse model of OPPG (Lrp5(-/-)), a mouse model of sclerosteosis (Sost(-/-)), and in mice with both genes knocked out (Lrp5(-/-);Sost(-/-)). Lrp5(-/-);Sost(-/-) mice have larger, denser, and stronger bones than do Lrp5(-/-) mice, indicating that SOST deficiency can improve bone properties via pathways that do not require LRP5. Next, we determined whether the anabolic effects of sclerostin depletion in Lrp5(-/-) mice are retained in adult mice by treating 17-week-old Lrp5(-/-) mice with a sclerostin antibody for 3 weeks. Lrp5(+/+) and Lrp5(-/-) mice each exhibited osteoanabolic responses to antibody therapy, as indicated by increased bone mineral density, content, and formation rates. Collectively, our data show that inhibiting sclerostin can improve bone mass whether LRP5 is present or not. In the absence of LRP5, the anabolic effects of SOST depletion can occur via other receptors (such as LRP4/6). Regardless of the mechanism, our results suggest that humans with OPPG might benefit from sclerostin neutralization therapies.