The duration dilemma in opioid agonist therapy.

OBJECTIVE: Studies dating back to 1964 consistently support the effectiveness of methadone as a maintenance treatment for opioid use disorder (OUD), and since 2003, the effectiveness of buprenorphine. Short-term detoxification has not proven to be an effective treatment, as it results in high relapse rates when compared with maintenance treatment with an opioid agonist therapy (OAT). The question about the duration of maintenance treatment for OUD has been debated with recommendations ranging from a minimum of 1 year, 2 years, to indefinitely. Other factors such as misconceptions, regulations, and insurance barriers also have an impact on the duration dilemma of OAT. DESIGN: There were no a priori criteria for article inclusion and this is not a structured literature review. It is a review of articles of convenience from 1964 to 2018. MAIN OUTCOME MEASURE: This paper aims to address the dilemma of the ideal duration of OAT and to discuss the factors that could affect this decision. RESULTS: Sustained OAT has had significantly better long-term outcomes than short-term detoxification or time limited maintenance. Optimal outcomes are dependent on adequate treatment duration. CONCLUSIONS: Addiction is a chronic brain disease and its treatment should be similar to the treatment of other chronic medical and psychiatric diseases. Long-term, sometimes lifetime, continuation of OAT for the treatment of OUD results in optimal outcomes when measuring morbidity and mortality. The accumulated evidence does not support any arbitrary limitation to the duration of OAT.

Patterns of opioid use during initial buprenorphine/naloxone treatment in relation to changes in opioid management laws in Kentucky.

BACKGROUND AND OBJECTIVES: There is limited information on the most commonly used opioid reported at the time of presentation for treatment with buprenorphine/naloxone and the extent to which state policy may impact type of opioid use reported. METHODS: Retrospective study, total N = of 595 from four different medical locations from January 1, 2009 to July 1, 2016 that provided buprenorphine/naloxone treatment in Louisville, Kentucky. Study aims included identifying the most commonly used opioid at the time of treatment before and after the creation of a state-wide opioid prescribing surveillance system (ie, the 2012 House Bill 1 [HB1]), and determine the extent to which clinical setting, sex, age, and insurance type impacted type of opioid reported during the intake appointment. RESULTS: Non-heroin opioid use decreased in the academic and private practice settings following passage of HB1, while heroin use increased in all three settings. After controlling for clinical setting and demographic characteristics, there was a significant increase in patients who reported using heroin (vs. non-heroin opioid) (RR = 25.00, p ≤ .001, CI = 12.08-51.73) and a significant increase in patients who reported using opioid agonists (vs. non-heroin opioid) (RR = 6.56, p ≤ .001, CI = 4.10-10.50) following enactment of HB1. DISCUSSION AND CONCLUSIONS: After the passage of HB1, there was a significant increase in patients reporting heroin use and opioid agonists compared to non-heroin opioids when presenting for treatment. SIGNIFICANT SIGNIFICANCE: There has been a notable shift in the opioid epidemic, which is evident in the outpatient treatment settings. (Am J Addict 2018;27:560-566).

Structure of aminodeoxychorismate synthase from Stenotrophomonas maltophilia.

PabB, aminodeoxychorismate synthase, is the chorismic acid binding component of the heterodimeric PabA-PabB complex that converts chorismic acid to 4-amino-4-deoxychorismate, a precursor of p-aminobenzoate and folic acid in microorganisms. The second component, a glutamine amidotransferase subunit, PabA, generates ammonia that is channeled to the PabB active site where it attacks C4 of a chorismate-derived intermediate that is covalently bound, through C2, to an active site lysine residue. The presence of a PIKGT motif was, until recently, believed to allow discrimination of PabB enzymes from the closely related enzyme anthranilate synthase, which typically contains a PIAGT active site motif and does not form a covalent enzyme-substrate intermediate with chorismate. A subclass of PabB enzymes that employ an alternative mechanism requiring 2 equiv of ammonia from glutamine and that feature a noncovalently bound 2-amino-2-deoxyisochorismate intermediate was recently identified. Here we report the 2.25 Å crystal structure of PabB from the emerging pathogen Stenotrophomonas maltophilia. It is the first reported structure of a PabB that features the PIAGT motif. Surprisingly, no dedicated pabA is evident in the genome of S. maltophilia, suggesting that another cellular amidotransferase is able to fulfill the role of PabA in this organism. Evaluation of the ammonia-dependent aminodeoxychorismate synthase activity of S. maltophilia PabB alone revealed that it is virtually inactive. However, in the presence of a heterologous PabA surrogate, typical levels of activity were observed using either glutamine or ammonia as the nitrogen source. Additionally, the structure suggests that a key segment of the polypeptide can remodel itself to interact with a nonspecialized or shared amidotransferase partner in vivo. The structure and mass spectral analysis further suggest that S. maltophilia PabB, like Escherichia coli PabB, binds tryptophan in a vestigial regulatory site. The observation that the binding site is unoccupied in the crystal structure, however, suggests the affinity may be low relative to that of E. coli PabB.