ABSTRACT
BACKGROUND AND OBJECTIVES: Non-prescribed substance use (NPSU) is a recognized phenomena exhibited by patients with substance use disorders while admitted to inpatient hospitals. What factors distinguish patients who engage in NPSU, or how their hospitalizations and outcomes differ, remains to be understood in full. Our study describes a cohort of medically admitted patients with substance use disorders with behaviors concerning for non-prescribed substance use (NPSU) during their hospitalization. METHODS: We extracted electronic health record data for all hospital encounters when an addiction consult was documented (n=3100). We defined NPSU cases during a clinical, interdisciplinary case review in which patients were deemed high risk based on team members' observations of one or more behaviors described in the NPSU Checklist. These individuals were placed on a "NPSU Protocol," which was implemented for optimization of care, destigmatization, and risk mitigation (n=61). We compared clinical characteristics, resource utilization, and treatment outcomes among the NPSU cohort to addiction consult patients without suspicion of NPSU but with stimulant or opioid use disorder diagnoses. RESULTS: Patients on the NPSU protocol were younger and had higher rates of infectious disease diagnoses reported during hospitalization than patients without concern for NPSU. Hospitalizations for individuals suspected of NPSU were longer, had higher rates of before medically advised discharge, as well as discharges without medications for opioid use disorder (MOUD). These outcome differences were also observed when analysis was restricted to hospitalizations in which an infectious disease was diagnosed. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Our study characterizes a population of people who exhibited behaviors concerning for NPSU and highlights key outcome disparities. To our knowledge, this study is the first to show a direct correlation between infectious disease diagnosis and NPSU, as well as a direct correlation between suspected NPSU and outcomes such as before medically advised discharge and discharge without MOUD, irrespective of infectious disease diagnosis. Further study is necessary to determine interventions to reduce poor outcomes among hospitalized patients with NPSU.
ABSTRACT
In autoimmune diseases, the accumulation of activated leukocytes correlates with inflammation and disease progression, and, therefore, the disruption of leukocyte trafficking is an active area of research. The serine/threonine protein kinase Tpl2 (MAP3K8) regulates leukocyte inflammatory responses and is also being investigated for therapeutic inhibition during autoimmunity. Here we addressed the contribution of Tpl2 to the regulation of macrophage chemokine receptor expression and migration in vivo using a mouse model of Tpl2 ablation. LPS stimulation of bone marrow-derived macrophages induced early CCR1 chemokine receptor expression but repressed CCR2 and CCR5 expression. Notably, early induction of CCR1 expression by LPS was dependent upon a signaling pathway involving Tpl2, PI3K, and ERK. On the contrary, Tpl2 was required to maintain the basal expression of CCR2 and CCR5 as well as to stabilize CCR5 mRNA expression. Consistent with impairments in chemokine receptor expression, tpl2(-/-) macrophages were defective in trafficking to the peritoneal cavity following thioglycollate-induced inflammation. Overall, this study demonstrates a Tpl2-dependent mechanism for macrophage expression of select chemokine receptors and provides further insight into how Tpl2 inhibition may be used therapeutically to disrupt inflammatory networks in vivo.