Creating a standard inpatient opioid withdrawal protocol.

Background: Despite safety and efficacy of medications for opioid use disorder, United States (US) hospitals face high health care costs when hospitalized patients with opioid use disorder (OUD) leave due to untreated opioid withdrawal.  Recent studies have concluded that evidence-based interventions for OUD like buprenorphine are underutilized by hospital services. Objective: We developed a practical opioid withdrawal protocol utilizing buprenorphine and the Clinical Opiate Withdrawal Scale to address opioid withdrawal during inpatient treatment of a primary medical condition. We are currently implementing this protocol at the UCLA hospital in Santa Monica. Design: The protocol includes order sets with appropriate and modifiable orders that can be submitted in the electronic medical record in order to deliver seamless care for opioid withdrawal. After the physician assesses the patient and initiates the protocol, nursing provides an essential role in continuing to monitor the patient's level of withdrawal and administering the appropriate medications in response. Inpatient pharmacy is instrumental in monitoring medication administration, as well as calculating and providing dosages for orders on Day 2 and 3 of the protocol. Collaboration with case managers is essential for providing appropriate resources and ensuring a safe discharge. Conclusion: Current challenges to widespread implementation of a standardized withdrawal protocol are discrepancies in addiction education across medical disciplines and inadequate outpatient access to buprenorphine providers and pharmacies that carry buprenorphine supplies.

Voting with their feet: Social factors linked with treatment for opioid use disorder using same-day buprenorphine delivered in California hospitals.

BACKGROUND: Medication for opioid use disorder (MOUD) using buprenorphine in primary or specialty care settings is accessed primarily by persons with private health insurance, stable housing, and no polysubstance use. This paper applies Social Cognitive Theory to frame links between social factors and treatment outcomes among patients with social and economic disadvantages who are seeking MOUD at California Bridge Program (CA Bridge) hospitals. METHODS: Electronic medical records for patients identified with OUD between January-April, 2020 receiving care at CA Bridge hospitals defined outcomes: hospital-administered buprenorphine; provision of buprenorphine prescription at discharge. Multi-level models assessed whether social factors-housing status, insurance type, and co-methamphetamine use-predicted outcomes while accounting for group-level effects of treating hospital and controlling for age, race/ethnicity, and gender. RESULTS: 15 CA Bridge hospitals yielded 845 patient records. Most patients received hospital-administered buprenorphine (58 %) and/or a buprenorphine prescription (55 %); 26 % received neither treatment. Patients with unstable housing had greater odds of hospital-administered buprenorphine compared to patients with stable housing. Patients with Medicaid had greater odds of receiving a buprenorphine prescription compared to patients with other insurance. Co-methamphetamine use was not associated with outcomes. CONCLUSIONS: Patients with OUD are successful in accessing same-day MOUD in CA Bridge hospital settings over a significant period. Importantly, access to MOUD in these settings was facilitated for patients traditionally not treated using buprenorphine, i.e., those with housing instability, Medicaid insurance, and co-methamphetamine use. Findings suggest barriers to MOUD for patients with social and economic disadvantages can be lowered by changing treatment delivery.

Defective response of CD4(+) T cells to retinoic acid and TGFß in systemic lupus erythematosus.

INTRODUCTION: CD25(+) FOXP3(+) CD4(+) regulatory T cells (Tregs) are induced by transforming growth factor ß (TGFß) and further expanded by retinoic acid (RA). We have previously shown that this process was defective in T cells from lupus-prone mice expressing the novel isoform of the Pbx1 gene, Pbx1-d. This study tested the hypothesis that CD4(+) T cells from systemic lupus erythematosus (SLE) patients exhibited similar defects in Treg induction in response to TGFß and RA, and that PBX1-d expression is associated with this defect. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from 142 SLE patients and 83 healthy controls (HCs). The frequency of total, memory and naïve CD4(+) T cells was measured by flow cytometry on fresh cells. PBX1 isoform expression in purified CD4(+) T cells was determined by reverse transcription polymerase chain reaction (RT-PCR). PBMCs were stimulated for three days with anti-CD3 and anti-CD28 in the presence or absence of TGFß and RA. The expression of CD25 and FOXP3 on CD4(+) T cells was then determined by flow cytometry. In vitro suppression assays were performed with sorted CD25(+) and CD25(-) FOXP3(+) T cells. CD4(+) T cell subsets or their expansion were compared between patients and HCs with two-tailed Mann-Whitney tests and correlations between the frequencies of two subsets were tested with Spearman tests. RESULTS: The percentage of CD25(-) FOXP3(+) CD4(+) (CD25(-) Tregs) T cells was greater in SLE patients than in HCs, but these cells, contrary to their matched CD25(+) counterparts, did not show a suppressive activity. RA-expansion of TGFß-induced CD25(+) Tregs was significantly lower in SLE patients than in HCs, although SLE Tregs expanded significantly more than HCs in response to either RA or TGFß alone. Defective responses were also observed for the SLE CD25(-) Tregs and CD25(+) FOXP3(-) activated CD4(+) T cells as compared to controls. PBX1-d expression did not affect Treg induction, but it significantly reduced the expansion of CD25- Tregs and prevented the reduction of the activated CD25(+) FOXP3(-) CD4(+) T cell subset by the combination of TGFß and RA. CONCLUSIONS: We demonstrated that the induction of Tregs by TGFß and RA was defective in SLE patients and that PBX1-d expression in CD4(+) T cells is associated with an impaired regulation of FOXP3 and CD25 by TGFß and RA on these cells. These results suggest an impaired integration of the TGFß and RA signals in SLE T cells and implicate the PBX1 gene in this process.