Lessons learned from the implementation of a medically enhanced residential treatment (MERT) model integrating intravenous antibiotics and residential addiction treatment.

BACKGROUND: Hospitalizations for severe infections associated with substance use disorder (SUD) are increasing. People with SUD often remain hospitalized for many weeks instead of completing intravenous antibiotics at home; often, they are denied skilled nursing facility admission. Residential SUD treatment facilities are not equipped to administer intravenous antibiotics. We developed a medically enhanced residential treatment (MERT) model integrating residential SUD treatment and long-term IV antibiotics as part of a broader hospital-based addiction medicine service. MERT had low recruitment and retention, and ended after six months. The goal of this study was to describe the feasibility and acceptability of MERT, to understand implementation factors, and explore lessons learned. METHODS: We conducted a mixed-methods evaluation. We included all potentially eligible MERT patients, defined by those needing ≥2 weeks of intravenous antibiotics discharged from February 1 to August 1, 2016. We used chart review to identify diagnoses, antibiotic treatment location, and number of recommended and actual IV antibiotic-days completed. We audio-recorded and transcribed key informant interviews with patients and staff. We conducted an ethnographic analysis of interview transcripts and implementation field notes. RESULTS: Of the 45 patients needing long-term intravenous antibiotics, 18 were ineligible and 20 declined MERT. 7 enrolled in MERT and three completed their recommended intravenous antibiotic course. MERT recruitment barriers included patient ambivalence towards residential treatment, wanting to prioritize physical health needs, and fears of untreated pain in residential. MERT retention barriers included high demands of residential treatment, restrictive practices due to PICC lines, and perceptions by staff and other residents that MERT patients "stood out" as "different." Despite the challenges, key informants felt MERT was a positive construct. CONCLUSIONS: Though MERT had many possible advantages; it proved more challenging to implement than anticipated. Our lessons may be applicable to future models integrating post-hospital intravenous antibiotics and SUD care.

Thyroid Progenitors Are Robustly Derived from Embryonic Stem Cells through Transient, Developmental Stage-Specific Overexpression of Nkx2-1.

The clinical importance of anterior foregut endoderm (AFE) derivatives, such as thyrocytes, has led to intense research efforts for their derivation through directed differentiation of pluripotent stem cells (PSCs). Here, we identify transient overexpression of the transcription factor (TF) NKX2-1 as a powerful inductive signal for the robust derivation of thyrocyte-like cells from mouse PSC-derived AFE. This effect is highly developmental stage specific and dependent on FOXA2 expression levels and precise modulation of BMP and FGF signaling. The majority of the resulting cells express thyroid TFs (Nkx2-1, Pax8, Foxe1, Hhex) and thyroid hormone synthesis-related genes (Tg, Tpo, Nis, Iyd) at levels similar to adult mouse thyroid and give rise to functional follicle-like epithelial structures in Matrigel culture. Our findings demonstrate that NKX2-1 overexpression converts AFE to thyroid epithelium in a developmental time-sensitive manner and suggest a general methodology for manipulation of cell-fate decisions of developmental intermediates.